PL93115B1 - - Google Patents

Description

The subject of the invention is a process for the preparation of new pyrimidines of the general formula I, in which R 1 is an alkoxy group with 1 to 3 carbon atoms, a morpholino, thiomorpholino, 1-oxyothiomorpholino or 1,1-dioxydothiomorpholino group or a piperazine group 4 may contain an alkanoyl group with 2 to 4 carbon atoms, an optionally substituted methoxy group, a carboxyl or acetyl group, or an amino carboxyl group, optionally substituted with one or two alkyl radicals with 1 to 4 carbon atoms or with a methoxymethyl radical, or in this position it contains a pyridinoyl, salicyloyl or furanoyl group or an alkylsulfonyl group of 1-3 carbon atoms, R2 is morpholino, thiomoflpholino, 1-oxydothiomorpholine or 1,1-dioxydothiomorpholino, or polyose substituted piperazine, optionally (4) an alkanoyl group with 2 to 4 carbon atoms, optionally substituted with an acetyl group, R 3 representing a hydrogen, chlorine or bromine atom, a nitro group , cyano, formyl or acetyl, and R 4 is a hydrogen, chlorine or bromine atom, a cyano group or an amino group, substituted with a cyclohexyl radical, a pyridyl radical or a phenyl radical, which is optionally substituted with a chlorine atom, a carboxyl group or a carbomethoxy group, or R4 is also a carhoalkoxy group with 2 to 4 carbon atoms, an alkyl radical with 1 to 6 carbon atoms, optionally substituted with 1 or 2 carboalkoxy groups with 2 to 4 carbon atoms, a hydroxyl group or a mercapto group, optionally substituted with an allyl radical or an alkyl radical with 1 to 6 carbon atoms, or is the 1-oxydothiomorphold group, as well as the physiologically acceptable addition salts of these compounds with inorganic or organic acids. The compounds according to the invention have valuable properties. pharmacological, especially anti-thrombosis, partly does not affect blood pressure, especially those compounds that are cyclized at the nitrogen atom of the piperazine ring, have no influence on the blood pressure. Compounds of formula I, in which all the symbols have the above meanings, are prepared according to the invention in such a way that the compound of general formula II, in which Rs as defined above, one or two X and Y and / or Z represent a convertible group such as a halogen atom, a hydroxyl group, a mercapto group or a sulfonic acid residue, a substituted alkyl, aralkyl or aryl hydroxyl, mercapto, sulfinyl group. or sulfonyl, and the remaining X, Y and / or Z are as defined above for R1, R2 and R4, is reacted with a compound of general formula (III) wherein A is as defined above for R19, Rg and / or R4. The cleavage group mentioned above is especially a halogen atom, such as a chlorine or bromine atom, a hydroxyl group, a mercapto group or a sulfonic acid group, a hydroxyl, sulfinyl or sulfonyl group, substituted with an alkyl, aralkyl or aryl radical, such as methoxy, ethoxy, phenoxy, methylthio, benzylthio, methylsulfonyl, methylsulfonyl or ethylsulfonyl. at a temperature of -20 ° C to 250 ° C, optionally in the presence of an acid-binding agent and preferably in a solvent such as dioxane, acetone, glycol dimethyl ether, dimethylformamide, dimethyl sulfoxide or ethanol, or in excess of the amine of general formula 3 used. however, carry out these reactions also without solvent. In the preparation of compounds of the general formula I, in which <R2 and / or R4 represent the 4 free piperazine group, it is preferable during the reaction to protect the imino group in the compound of the general formula II and / or imdnance in the appropriately substituted amine of the general formula III in a known manner, n and p. with an acyl group such as a carboethoxy, formyl, acetyl or benzoyl group. This protecting group can then be cleaved again, e.g. hydrolytically in the presence of an acid or a base, at or below the boiling point of the solvent used. The cleavage of the acyl group in the S-oxidic compounds, however, is preferably carried out by hydrolysis in the presence of a base, e.g. potassium hydroxide. If a compound of the general formula I containing a thiomorpholino group is obtained in the process of the invention, then this compound can be oxidized by oxidation. convert to the corresponding S-oxide or S, S-dioxide, and if the obtained compound of general formula I contains a piperazine group whose imino group is substituted with an acyl group or an aminocarbonyl group, then the hydrolysis route can be converted into a corresponding compound piperazine of the general formula I not substituted in the 4-position. If the obtained compound of the general formula (I) contains a free imino group, it can be converted by acylation or carbamoylation into the corresponding compound of the general formula (I), and if obtained the compound of the general formula (I) contains a hydrogen atom in the 5-position, and by nitration this compound can be converted into a corresponding compound The oxidation process, if desired, is carried out preferably with customary oxidizing agents such as hydrogen peroxide, peracetic acid, sodium periodate or potassium permanganate, preferably in a solvent, for example acetic acid, in particular at a temperature of 0 ° - -80 ° C. If oxidation with, for example, hydrogen peroxide, peracetic acid or sodium periodate, the S-oxoate compound of the general formula I is preferably obtained, but if oxidized with potassium permanganate, the S, S compound is preferably obtained. The dioxide formula 1, if necessary, hydrolysis is carried out in the presence of a base such as sodium or potassium hydroxide or an acid such as hydrochloric acid, preferably in a solvent such as water, ethanol, isopropanol or ethanol with water and Preferably at the boiling point of the solvent used (for example at 80-10 ° C. Any acylation to be used is preferably carried out with a suitable carboxylic acid in the presence of a water-repellant such as, for example, N, N-dicyclohexylcarbodiimide. or thionium chloride, or by means of a reactive carboxylic acid derivative, for example by means of a "halide, anhydride, ester or mixed anhydride, optionally in the presence of a base, such as sodium carbonate, triethylamine or pyridine, preferably in a solvent such as ether, dioxane, benzene or pyridine and at a temperature of 0 ° -100 ° C. Any nitration of the compound obtained is carried out with a nitrating agent such as nitric acid with sulfuric acid or nitric acid alone, at elevated temperature, nip. 50-80 ° C. The compounds of formula II used as starting products are partly known from the literature or can be prepared by known methods (see examples). In this connection, it is possible to produce a compound of the general formula I containing only one or two exchangeable groups from a preliminary starting product having several exchangeable groups in the diaper ring by reacting with a compound of the formula III. On the other hand, it is also possible, in the compound of general formula II, to additionally transform such groups X, Y and / or Z which are not (exchangeable groups, e.g. the thiomorpholinopyrimidine group can be additionally oxidized, the formylpiperazine group can be additionally deacylated or Also, the exchange of the exchangeable group by a group with an even greater reactivity makes it possible to prepare starting compounds of the formula 2. The compounds of the general formula I obtained can, if necessary, be converted into salts with physiologically acceptable acids. for example, such as hydrochloric, hydrobromic, sulfuric, phosphoric, fumaric, succinic, lactic, citric, tartaric or maleic acids. As mentioned in the introduction, the compounds according to the invention have valuable pharmacological properties, and in particular They strongly inhibit the formation of clumps of blood platelets and their ability to adhere. The ability to counteract clumping of blood platelets can be demonstrated, for example, by the method Born and Cross and [J. Pnysiol. 170, 397 (1964)] or the method of K. Breddin {Schweiz. Med. East 95, 655-600 (1965)], and the effect on adhesion ¦ is determined by a so-called hold test, eg the Morris method (E). Deutsch, E. Ger¬lach and K. Moser: 1. Interndbionales Symposiura liber Stoffwedhsel und Mernbranpermeabilitat von 40 45 50 55 605 93 115 6 Erythrozyten und Thrombozyten, Wieden 1969, edited by Georg Thieme, Stuttgart /. The Born and Morris method was studied e.g. the following compounds: A = 6-methyl-5-nitro-2'-piperazine-4- (1-oxy thymorpholine) -pyrimidine, B = 6Hiiethyl-5-nitro-2-piperazine-4-thiomorpholine-pyrimidine, C = 5-cMoro-2-piperazine-4- (1-oxido-• thiomorpholine) -6-pyrimidinecarboxylic acid nitrile, D = 6-ethcksy-5-nitro-4- / 1-oxydothiomorpholine / -2-piperazinopyrimidine , E = 5-nitro-4- / 1-oxydothiomorpholine / -2-piperazine-6-iscpropoxypyrimidine, * F = 6-II-order butoxy-4- / 1,1-dioxydothiomorpholine / -5-nitro -2- »piperazinopyrimadine, G = 6-methylthio-5-niltro-4- / lo: xydothiomoitfoline / -2-formylpiperazinopyrimidine and H = 6-methyl-5-ndtro-4- / 1-oxydothiomorpholine / -2 - -acetoacetylpiperazinopyrimidine. 1. Determination of platelet aggregation by the Morris method. In order to determine the ability of the test substances to counteract the formation of sticky blood platelets, a pipette of 1 ml of human blood is pipetted into small test tubes and the amount of the test substance is added in such an amount that the final concentration is 10 ~ 5 mol / liter or 1 × 10 ~ 5 moles / liter. The test tubes are cultured at 37 ° C for minutes, then half of the test tubes are filled with 1 g of glass pearls (gas chromatography glass pearls from BDH Poole, Great Britain) and the sealed test tubes are then attached to a disc. rotating about a horizontal axis and rotating the discs within 1 minute, causing the glass pearls to come into contact with the blood. Then (blood is left in the same test tubes for a further hour at room temperature, with satisfactory deposition of red blood cells. From the plasma constituting the upper layer, samples of 0.01 ml are taken and diluted with a solution to celloscopic examinations in the ratio of 1: 8000 and count the plates with the telescope, determining the percentage reduction in adhesion under the influence of the test substance, compared with the results obtained for test tubes without glass pellets. The average results of 4-6 tests are given in the table. Fig. 2. Determination of platelet aggregation (blood by Born and Gross method. The platelet aggregation in the blood plasma of healthy individuals containing a significant amount of these platelets is measured, photometrically measured and the course of the decrease in optical density following the addition of adenosine diphosphate) is measured. From the angle of the slope of the density curve, the aggregation velocity of the plates is determined, with the point on the curve which corresponds to the highest permeability light, is used to calculate the "optical density". The doses of adenosine diphosphate are used as small as possible, but such that they cause irreversible clustering. Prior to the addition of adenosine diphosphate, the plasma samples are cultured at 37 ° C for 1 minute, with the addition * of various amounts of the test substances. 3. The acute toxicity of test compounds is determined in mice with observations over 14 days, partly as a guideline, or the LD50 is determined from the percentage of animals that die during the observation after receiving different doses (see J. Pharmacol. exper. 96, 99 (1949)]. The results are also given in the table. Table Test substance ABCDFG 1H Morris% inhibition test at 10 millimoles / liter 92 66 92 100 69 61 2 11+ Born test with adenosine diphosphate EC50 1 , 2X10-8 3X10 ~ «1.3X10-7 2.5X10-8 2X10-7, 8.5X10-7 5X10-6 io-4 LD50 mg / kg IV 160 70 101 150 170 150 Oral 600 620 836 600 500 1500 1000 1000 * / Concentration 30 millimoles / liter. In the Born test, the EC50 also denotes the concentration in moles / liter which produces a 50% change in "optical density". For pharmacological purposes, compounds of general formula I or their the salts can be used together with other active substances in the form of preparations such as dragees, tablets, suppositories or solutions, and these preparations are prepared by known methods. A single dose of these compounds for adults is 10-500 mg. , preferably 20-150 mg. The invention is illustrated in the following Examples, the Lettered Examples describing the production of the starting products, with and the Roman numeral examples describe the process according to the invention. Example A. 2-, carboethoxypiperazine-4-chloro-6-amino-pyrimidine. 29.0 µg of 2,4-dichloro-6-aminopyrimidine, EH. Bretsehneider et al. Monatsh. f. Ohemie 92, 132 (1961)] is mixed with 150 ml of dioxane, the resulting suspension is heated to 80 ° C and treated with 60.2 g of N-carboethoxy piperazine and then left for 40 minutes at this temperature. The mixture is then poured into 500 ml of water while stirring in an ice bath. The product is initially oily and crystallizes after about 150 minutes. It is filtered off and crystallized from 300 ml of methanol to obtain 28.8 g of 2-carboethoxy-4-chloro-6-aninopyrimidine, temperature 163-166 ° C, which is 57.3% of the yield. theory. Example B. 2-canboethoxypiperazine-4,6-dichloropyrimidine. 79.0 g of 2-methylthiobarbituric acid [Koppel, Springer and Robins, J. Org. Chem. 26,792-803 (1961)] and 94 g of carboethoxypiperazine in 1100 ml of dimethylformamide are heated at 120 ° C for 3 'hours, during which methyl mercaptan is released. It is then cooled, diluted with water, and stirred until 2-carbohydrate-xytpyrimidine-4.6% uhydrolide crystals are obtained. O - 68.6 g of product are held, which is 51.4% of theory. 3.4 g of the crude product obtained are boiled with 92 ml of phosphorus oxychloride for 1.5 hours and then evaporated to dryness. The residue is stirred with ice, the precipitate is filtered off and refluxed with ethanol for 4 hours in order to completely convert the simultaneously produced 2-chlorocytibonylpiperazine-4,6-dichloropyrimdine into 2-carboxy-piperazine. -4,6-dichloro-pyrimidine, the progress of the reaction being monitored by thin-layer chromatography on a silica gel plate, eluting with n-pentane / ethyl acetate 7: 3. After evaporating the alcoholic solution, the product is obtained in the form of white crystals. 37.9 g of product are obtained, mp 136-143 ° C., which is 49% of theoretical yield. 4-thiomorphodine-2,6-rimidine. 271 g of 2,4,6-trichloro-pyrimidine are dissolved in 1.8 liters of acetone and, while stirring, slowly poured into a mixture of 250.3 g of triethylamine and 170.5 g of thiomonpholine in 0.7 liters of acetone so that the temperature the mixture did not rise above 40 ° C. Stirring was then continued for 46 minutes, the temperature dropping back to 30 ° C. The precipitated triethylamine hydrochloride is filtered off, washed with acetone, and the filtrate is evaporated in a rotary evaporator. The residue is recrystallized from 2.3 l of ethanol to give 222.7 g of 2,6-dichloro-4-thiomorpholinopyrimidine as white crystals. The product is recrystallized again from 2.2 liters of ethanol, the first fractions being 196.15 g of pure white crystals. After thickening of the mother liquor, an additional 17.9 g of product is obtained, so a total of 214.4 g of product is obtained, which is 57.1% of the theoretical yield. The product melts at 118-121.5 ° C. Example D. 2-thiomorpholine-4,6-dichloropyrimidine. From the mother liquor obtained after the first crystallization in the process described in example C, the simultaneous quantitatively 2-thiomorpholine-4,6-dichloropyrimidine is obtained. To this end, the mother liquor is evaporated and the residue is chromatographed on a silica gel column with grains 0.2-0.5 mm / W, eluting with toluene at a substance to silica gel ratio of 1:10. The first fractions contain the total amount of the product. The yield of 79.0 g is 21.0 t / the theoretical amount. The product melts at 79.5-81.5 ° C. Example B. 2-PhonylpiperaseiK * 4Vl-oxy-thymorpholine / -5-nitro-6-chloropyrothymidine. 100 g of 2-formylpyipeffase Thio-4-thiomorph61ino-6-chloropyrimidine with a melting point of 195 ^ -1Q & ° C is added in portions, while stirring, to 570 ml of concentrated sulfuric acid, keeping the temperature of the mixture at about 20 ° C with occasional cooling. until the starting material dissolves completely, which takes about 30-10 minutes, then it is cooled to 0 ° C. 115 ml of fuming nitric acid are slowly added dropwise to the solution, keeping the temperature at about 5 ° C by cooling well with ice. . After completion of the dropwise addition, the product is stirred for an additional 20 minutes and the resulting cold yellow solution is mixed with about 3 liters of crushed ice, whereupon the greasy yellow product is precipitated. The product is extracted with 1.2 liters of chloroform and then step 2 0.7 liter each of chloroform, the combined extracts are dried over sodium sulfate and evaporated on a rotary evaporator. The yellow resinous residue is dissolved in 1.1 liters of hot ethanol, cooled slowly to -30 ° C and seeded with crystals. Stirring is continued for 1 hour at room temperature, then cooled with ice water until crystallization is complete. After 20 minutes, the product, having a temperature of about 5 ° C, is filtered off, the precipitate is washed with cold ethanol and dried in a desiccator over sulfuric acid. 104 g of product with a melting point of 176-178 ° C are obtained, which is 87.74% of theoretical yield. In a similar manner, from 6-ethoxy-2-piperazine-4-thiomorpholinopyrimidine and concentrated sulfuric acid with concentrated sulfuric acid. nitric acid gives 6-ethoxy-5-nitro-4- (1-oxydothiomorpholine) -2-piperatinopyrimidine. Before extraction with the chlorophore, the pH of the mixture is adjusted to 9 with sodium hydroxide. The product recrystallized from ethanol melts at 223-224 ° C. nitro-6-cyclohexylaminopyrimidine. 14.0 g of 2-methylomer'-capto-4,6-dichloro-5-nitropyrimidine / Brown and Jacobsen, Soc. 1963, 3776 / are dissolved in 200 ml of methanol, cooled to -60 ° C and treated with 6.0 g of triethylamine, and then 4.0 g of cyclohexylamine is added dropwise during 1 hour with stirring so that the temperature of the mixture is it was not higher than -60 ° C. Then methanol was distilled off, the residue was dissolved in chloroform and washed five times with water, then chloroform was distilled off and the residue was recrystallized from isopropanol to give 11.2 g of 2-methyl-mercapto-4-chloro-5-nitro. 6-cycloiiexylamino-pyrimidine, which is 62% of theoretical yield. Produifct melts at 98-104 ° C. 3.0 g of the product obtained are dissolved in ml of acetone, a solution of 1.38 g of potassium carbonate in 1.5 ml of water is added and treated with a solution of 1.2 g of thiomorpholine in 10 ml of acetone. The mixture is then stirred thoroughly at room temperature, after a short time a large volume of crystalline precipitate is formed, which increases with the addition of water. This product is filtered off and recrystallized from isopropanol to give 2.3 g (G2% of theory) of 2-methylmercapto-4-thiomo (rfoHno-5-nitro-6-cyclohexyldaminopyrimidine, m.p. 145-146 °). C. Example G. 2- (1-Oxydothiomorphoiino) -4-formylpiperazine-5-nitro-6-chloropyrimidine. This compound is prepared in a manner analogous to that described in Example E, from 2-thiomorpholine-4- -foimylpiperazine-chloropyrimldine and mixtures of fuming nitric acid with concentrated sulfuric acid. The product melts at 110 ° C-L3 ° C9 and the yield is 89.4% of theoretical. • Example H 2-thiomorpholine-4. chloropyrimidine and 4-thiomorphohno-2-chloropyrimidine. To a solution of 8.0 g (0.054 mol) of 2,4-di-chloropyrimidine in 1330 ml of acetone is added dropwise while stirring at -35 ° C, a solution of 6.1 g / 0.059 moles of thiomorpholine in 15 ml of water and a solution of 8.1 g (0.059 moles) of potassium carbonate in 15 ml of water, followed by stirring for 2.5 hours at a temperature at room temperature, acetone is evaporated under reduced pressure. pressure, the residue is rinsed with water, dried and ohromatographised on 250 g of silica gel of activity class I, grain size 0.05-0.2 mm, eluting with benzene and ethyl acetate 5: 1. The substance with high RF value is 2-thiomor- folinopyrimidine, which, after recrystallization from isopropanol, melts at 64-65 ° C. 0.7 g of product is obtained, which is 6% of theoretical yield. The low RF substance is 4-thiomorpholine-2-chloropyrimidine which melts at 106-108 ° C upon recrystallization from isopropanol. 8.9 g of this compound are obtained, which is 77% of theoretical yield. The following compounds are prepared in an analogous manner: a) 5-cyano-2,6-diwucMoro-4-thiomorpholine with a melting point of 180 ° C, with a yield of 41.7% of the theoretical yield, -cyano-4,6-dichloro-2-thiomorpholino-pyrimidine, melting point 99 ° C, with a yield of 4.5% of theoretical yield, 5 being used as starting products. cyano-2,4,6-trichloropyrimidine and thiomorpholine and b / 5-cyano-2,4-dichloro-methoxypyrimidine with a melting point of 1T7 ° C, with a yield of 29.4% of theoretical yield and 5-cyano-4.6 -dichloro-2-methoxypyrimidine, melting point 156 ° C, yield 10% of theoretical yield, if 5-cyano-2,4,6-tri-moropyrim is used as starting products; idine and methanol and the reactions are carried out by for 20 hours at 65 ° C, without addition of potassium carbonate. Example I. 6-ethoxy-4-chloro-2-methylthio--5-nitropyrimidines and. 24 g (0.1 mole) (4,6-dichloro-2-methylthio-5-nitropyrimidine) for preparation see Brown, Jacobsen, J. Chem. Soc. 1965, 3776) is mixed with 200 ml of ethanol at 0 ° C., and the resulting suspension is added dropwise with stirring at 0 ° C. for 20 minutes, a solution of sodium ethanol prepared from 2.35 g (0.102 grams of atom). / sodium and 80 ml ethanol, then stirring continued for 45 minutes at 0 ° C. The reaction mixture is then poured into 700 g of crushed ice, the separated yellow crystals are filtered off, dried and recrystallized from gasoline with a boiling point of 60-100 ° C. 20.8 g (3.5% of theory) of 6-ethoxy-4-chloro-2-methylthio-1-nitro-pyrimidine with a melting point of 83-65.6 ° C. 6-dichloro-2-methylthio-5-nI-pyrimidine with the corresponding sodium alkoxide, the following compounds are prepared: sa (4-chloro-6-me'toxy-2-methylthio-5-nitropyrimidine, which after recrystallization from gasoline melts at 77.5-79.5 ° C, b) 4-chloro-2-methylthio-5-nitro-6-n-propoxypyrimidine, oily consistency, Rf = 0.4, purified on silica gel by elution with benzene from gasoline 1: 1, c) 4-chloro-6-isopTopoxy-2-methylthio-5-nitropyrimidine, which, recrystallized from gasoline, melts at 55-57 ° C. , d (6-allyloxy-4-chloro-2-methyltho-6-nitropyrimidine, melting point SI-52 ° C and boiling point 145-1489 ° C / 0.2 mm Hg, e) 6-n-4 -chlbro-β-methylthio-5-nI-tropyrinidine oily consistency, RF = 0.45 after purification on silica gel with eluting with benzene from gasoline 1: 1, i.e. 6-II-order-butoxy-4-cMoxo-methylthio-5-n5-tropyrimidine oily, RF = 0.45 after chromatography on silica gel using gasoline and ethyl acetate 1 : 1 g / 4-c1yloro-2-methylbothi-neopentyyloxy-5-niitropyrimidine, boiling point 98-103 ° C / 0.01 mm Hg. Example J. 6-ethoxy-2-methylbithium-4- / l -oxy-thymorpholine / -5-nitropyrimidine. g (0.06 moles) of 6-ethoxy-4-cMoro-2-methyloylos-5-nitropyrimidine and 5 g of potassium carbonate are mixed with 150 ml of ethanol, and a solution of 7.8 g / 0.066 g / 0.066 is added to the suspension obtained. mole (1-oxydothiomorpholine) in 100 ml of ethanol, then the mixture is refluxed at 0 ° C for 4 hours. The mixture is then poured into ice-water, the yellow crystals are filtered off, dried and recrystallized from ethyl acetate by adding activated carbon. 17.7 g (88.5% of theory) of 6-ethoxy-2-methylthio-4- (1-oxydothiomorpholine) -5-nitropyrimidine are obtained at 160 ° -162 ° C. The following procedure is prepared in an analogous manner. Compounds: a / from 6-ethoxy-4-chloro-2-methylthio-5-ntropyrimidine and thiomorpholine gives 6-ethoxy-2-methylthio-4-thiomoitpholine, 5-nitropyrimidine, which is crystallized from acetate Ethyl ethyl / gasoline melts at 117.5 ° -10.5 ° C, b) 6-ethoxy-4-chloro-2-methylthio-5-nitropyrimidine and 11 Voxydothiomorpholine gives 6-ethoxy-methylthio-5- niitro-4 (l, 1-dioxydothiomorpholine) -pyrimidine, m.p. 100 - tó -? 163 ° C (from ethyl acetate), c) from 6 - oxy-4-chloro-2-methylthio - 5-nitropyrim- dynes and morpholines are obtained from 6-ethoxy-2-methylthio-4-orpholine-5-nitropyrimidine, m.p. 114.5 ° C 1160 ° C (from ethanol), 60 ° C from 4-chloro-6-methoxy-2-meth 'Tylothio-, 5-nitropyrimine and 1-oxydothiomorpholine, by reaction at 20 ° C for 15 hours, gives ie 6-mefcoxy-fl-methylthio-5-nitro-4- (1-oxido & - morpholine) -pyrimidine, m.p. ", 175 ^ 177.5 ° C / from ethanol /, 5093115 11 e / from 6-allyloxy- 4-chloro-2-methyl-1; o-5-nitropyrimimine and thiomorpholine by reaction at 20 ° C for 2 hours gives 6-alldloxy-2-methyl, thio-5-nitro -4-thiomorpholinopyrimidine, m.p. 89 ° -90.5 ° C. (from petrol, bp 60 ° -80 ° C.), 6-allyl-4-chloro-2-methylthio-5-nitropyridine and 1,1-Dioxydothiomorpholine is reacted at 20 ° C for 2 hours to produce 6-αUiloxy-4- (1,1-dioxydothiomorpholine) -2-methylthio-5-nitropyrimidine at a temperature of mp 147-149 ° C (from gasoline boiling at 60 ° -0 ° C mixed with ethyl acetate in the ratio 2: 3),% from 4-chloro-2-methylthio-5-nitro-6-n-propoxypyrimidine and 1,1-Dioxydothiomorpholines are obtained from 4- (1,1-dWiUoxydothiomorphoh'no) -2-methylthio-5-nitro-tf ^ n-propoxypyrimidine with a melting point of 160-1 "fl2 °. C (from isopropanol), h) from 4-chloro-2-methylthio-5-ni'tro-6-n-propoxypyrimidine and 1-oxydothiomorpholine, gives 2-methyl1; io-5-ni: tr-4 - (1-Oxydo thiomorpholino), 6-n-propoxypyritifidine, m.p. 146 ° C and 48 ° C (from isopropanol), and / from 4-chloro-2-methylthio, 5-nitro-6-n-propoxypyrimine and thiomorpholine is obtained August 2-methylthio-n-indiTo - N-propoxy-thiomorpholinopyrimidine, m.p. 76-78.5 ° C (from ethanol) and / from 4-chloro-2-methylthio-5-nitro-6-n -propoxypyrimidine and morpholine are obtained 2-methylthio-4-morpholine-5-nitro-16-n-pixpoxypyrimidine with a boiling point of 89 ° -90 ° C. (from isopropanol), k) from 4-chloro-2- methylthio-5-nitro-6-isopropoxypyrimidine and 1,1-dioxydothiomorpholines are obtained with 4- (1,1) diolkoxydothiomorphol (-2-methyl, thio-5-nitro-6-isopropoxypyrimidine, mp 168) -170 ° C / from isopropanol /,, 1 / from 4-cMoro-2-methylthio-5-nitro-6-isopropoxypyrimidine and xydothiiomorpholine, 2-methylthio-5-nitro-4- (1-oxy) is obtained tothiomorpholine (-6-isopropoxy-pyrimidine, mp 127— -129 ° C) (from isopropanol), m / from 4-chloro-2-methylthio-5-riitro-6-isopropoxy-pyrimidine and thiomorpholine, 2-methyl- thio-5-ni'tro-6-isopropoxy-4-thiomorpholmopyrimidines, m.p. 97-98.5 ° C (from -benzyl), including 4-chloro-2-methylthio-5-nitro. 6-isopropoxypyrimidine and morpholine are obtained from 2-methylthio-4-morpholine-5-nitro-6-isopropoxypyrimidine with a melting point of 80-81 ° C. (from gasoline) and from 6-n-butoxy-4. -chloro-2-methylthio-5-nitropyrimidine and 1,1-dioxydothiomorpholines are obtained 6-n-butoxy-4- (1,1-dioxydothiomorpholine) -2-methylthio-5-nitropyrimidine with a melting point of 128 -130 ° C, (from ethanol), p) from en-butoxy-4-chloro-methyl-S-nitropyrimidine and 1-oxydothiomorifoline, 6-n-butoxy-2-methylthio-5-nitro-4 is obtained - (1-oxydothiomorpholine) -pyrins -130.5 ° C (from ethanol), q) from 6-n-1-butoxy-4-chloro-2-methylthio-5-nitropyrimidine and thiomorpholine, 6-n -ibuto » x-2-methylthio-5-nitro-4-thiomorpholinopyrimlidine, mp 107-109.5 ° C (from cyclohexane), from 6-n-butoxy-4-chloro-2-methylthio-5-nitropyr - midines and morpholines are obtained from 6-n-butoxy-2-methylthio-4-morpholine-5-nitropyrimidine, mp 98-1'00 ° C (from cyclohexane), for example 6-II-butoxy- 4-chloro-2-methylthio-5-nitropyrimidine and 1,1-dioxydothiomorpholine are obtained 6-II-order butoxy-4- (1,1-dioxydothiomorpholine) -2-methylthio-5-nitropyrimidine with a melting point of 1162.5-1-4.5 ° C (from ethanol), i.e. 6-toutoxy-4-cbloro-2-methylthio-5-nitropyrimidine and l-oxydothiomorpholine, 6 -II-rzedjbuitoxy-2-methylthio-§-nitro-4- (1-oxydo-thiomortpholine) -pyrimidine, m.p. 121.5-123 ° C (from ethanol), in (6-II-order butoxy-4) -chloro-2-methylthio-5-nitropyrimidine and thiomorpholine are obtained 6-II-butoxy-methylthio-S-nitro-thiomorpholthio-pyrimidine, mp 87.5-89.5 ° C. / from cyclohexane /, v / from 4-chloro-2-methylthio-6-neopentoxy-5-nitro-pyrimidine and 1-oxythiomorpholine, we get 2-methylthio-6-neopentoxy-5-nrtro-4- / 1-olxydothio - 2B morpholino / -pyrimdine, m.p. 125-127 ° C / from diisopropyl ether / and from 4-chloro-2-methylfcio-6-neopentoxy-5-niltro-pyrimidine and thiomorpholine is obtained from 2-methyl-thio -6-neopentoxy-5-nitro-4-thiomorpholinopyrimidine, mp 102-104 ° C (from ethanol). Example K. e-chloro-E-methylthio-S-nitro-4- (1-oxydothiomorpholine) ipyrimidine. 36 g / 0.15 mol / 4,6-dichloro-2-methylthio-5-nitropyrimidine is dissolved in 100 ml of acetone and added dropwise to the solution, after cooling to -50 ° C, while stirring 35.7 g / 0.3 mole of 1-oxyothiomorpholine, then stirred for a further hour and then poured onto ice, the precipitate formed was filtered off, dried and recrystallized from ethyl acetate to give 6-chloro-2-methylthio. -5- niltro-4- (l-oxydbthiomorpholine) -pyrimidine, mp 160-102 ° C. The yield of the process is 80.4% of theoretical yield. The following compounds are prepared in an analogous manner: a / from 4,6-dichloro-2-methylthio-5-nitropyrimidine and thiomorpholine by reaction at -50 ° C for 80 minutes, 6-chloro -2-methylthio-5-nitro-4-thiomorphollinoprimidine, m.p. 138-140 ° C, is obtained from a mixture of gasoline and ethyl acetate 2: 3 (b) with 4,6-two chloro-2 4-amino-6-chloro-2-methylthio-5-n-tropyrimidine with a melting point of 176-177.5 ° C (from carbon tetrachloride) is obtained from methyl 5-nitropyrimidine and concentrated ammonia. Example L . 6-amino- &Lt; 2-methylthio-5-nitro-4- (1-oxydothiomorpholino) &lt; 3 &gt; 3.08 g (0.014 mol) of 4-chloro-4-amino-2-methylthio-5-nitropyrimidine are dissolved in 50 ml of acetone 60 and a solution of 3.2 g / 0.027 mole of 1-oxydothiomorpholdin in 20 ml of acetone, the mixture is stirred for 1.5 hours, and then ice is added to the mixture. The resulting precipitate is filtered off and recrystallized from ethanol to give 6-amino-2-methyl-13 lotions. <5-nitro-4- / l-oxydothiomorphOlino / -pyrimidine with a melting point of 239 ^ 242 ° C, yield 7 (8 * 2% of yield (theoretical. Example M. 2- / N-carboethoxyp4rperazine / - - 4,6-dihydroxy-5-nitroipyrinidine. 100 g (0.493 mol) 2,4-dihydroxy-2-methylthio--5-riitropyrimidine (prepared by the method of Brown, Jacobsen, J. Chem. Sec. 1965, 3776 (along with 156) g (0.986 moles) of N-carboethoxypiperazine is heated with stirring at 120 ° C for 30 minutes, after which the solidified reaction mixture is recrystallized and, with further treatment from ethanol, obtaining 140.5 g (91.1 l). % Of theoretical yield (2'-N-carboethoxy-piperazine) -4,6-dihydroxy-5-nitropyrimidine, m.p. 220-2.24 ° C. In an analogous process, from 4,6-dihydroxy-2- Methylthio-5-nitropyrimidine and thiomorpholine are 4 ^ 6-dihydroxy-5-nitro-2-thiomorpholinopyrimidine with a melting point of 220-223 ° C. Example N. 4-i6-dichloro-5-nitro-2 -thiomorpholinopyrimidine. For mixtures 1100 ml of phosphorus oxychloride and 190 ml of diethylaniline are added portionwise 19.0 g (0.735 mol) of 2J4-dihydroxy-5-nitro-2-thiomorpholinopyrimidine, the temperature of the mixture rising to 60 ° C. The mixtures are then boiled under reflux for 3 hours, then 600 ml of phosphorus oxychloride are distilled off and the residue is carefully poured onto ice. The aqueous phase is extracted with chloroform, dried over sodium sulphate, combined with activated carbon and evaporated to dryness. The residue is recrystallized twice from gasoline / gasoline, yielding 44 g (2K), 4% of theoretical yield (4,6-dichloro-5-nitro-2-thiomorpholine-pyrimidine with a melting point of 164-105 ° C. (N-carboethoxy-piperazine) -4, 6-dihydroxy-5-nitropyrimidine and phosphorus oxychloride gives 2- (N-perazine), 4- dichloro-nitropyrimidine with a melting point of 120-1121.5 ° C / from gasoline /. Example O. '6-ethoxy-4-chloro-5-nitro-2-thiomorphoMnopyrimidine. 14.6 g (0.05 mol / 4.6 g) of diohaoro-5-nitro-2f-thio-morpholinopyrimidine are dissolved in a mixture of 200 ml of acetone and 200 ml of dioxane, the solution is cooled to -20 ° C and At temperature, sodium ethoxide solution prepared from 1.15 g (0.05 mole) of sodium and 100 ml of ethanol was added dropwise to the solution. The mixture was then stirred at room temperature for 1 hour, poured onto ice, filtered off the precipitate and recrystallized from isopropanol to give 10.3 g (67.5% of theory) of 6-ethoxy-4-. chloro-5-nitro-2-thiomorpholinopyrimidine, mp 149-150 ° C. Example P 2- (N-cariboethoxypiperazine) - -6-Moro-tiomorpholinopyrimidine. 7.0 g (0.02 mole) of 2- (N-carboethoxypiperazine) -4, € - -dichloro-5-nitropyrimidine are dissolved in 100 ml of acetone, and the solution is added dropwise to the solution at -40 ° C. 5 g of potassium carbonate and then with stirring a solution of 2.1 g (0.02 mole) of thiomorpholine in 30 ml of acetone. Then the mixture is stirred at the temperature of -40 ° C for 2 hours, then additionally at room temperature for 1.5 hours, poured onto ice, the obtained precipitate is filtered off, dried and recrystallized from gasoline / acetate of ethyl alcohol, obtaining 5.3 g (64.7% of theoretical yield) (2- (N-carboethoxypiperazine) -6-chloro-4-thiomorpholinopyrimidine with a melting point of 134.5 ° 1 & 6.5 ° C. Example Q 6-ethoxy-2-piperazine-4-thio, morpholinopyrimidine. 9 g (0.03 mol) of 6-chloro-2- (N-formylpiperazine) -4-thiomorpholinopyrimidine, mp 196-201 ° C., are added to the sodium ethoxide solution prepared from 2.3 g / 0. 1 mol of sodium and 150 ml of ethanol, then the mixture is heated in an autoclave for 2 hours at 220 ° C. After cooling, the mixture is poured into water, extracted with chloroform, dried over sodium sulfate and evaporated to dryness. The remainder is purified by chromatography on silica gel 0.2 to 0.5 mm from Merck, eluting with a 9: 1 mixture of chloroform and methanol. The homogeneous fractions are combined and evaporated to give 6.8 g (72.7% of theory) of 6-ethoxy-2-piperazine-4-thiomorpholinopyrimidine. Example R. 5-carbamoyl-2,4,6-tri-hydroxy - pyrimidine. This compound is prepared by the method of HC Scarborough, WA Gould, J. Org. Chem. 26, 3720/1961 / M from barbituric acid and urea / 3 hours at 160 ° C /. A product with a melting point of 350 ° C. is obtained in 87.7% of theoretical yield. In a similar manner, 5-carbamoyl-4.6 is obtained from thiobarvitric acid and urea (3 hours at 170 ° C.). - dihydroxy-2-thio-pyrimidine, m.p. 350 ° C. Example S. 54-carbamoyl-4,6-dihydrofcsy--2-methylthio-pyridine. For a solution of 4.2 g (0.15 mol) sodium hydroxide in 150 ml of water, 5.6 g (0.03 mole) of -caribamoyl-4 y6-dihydroixy-2-thiopyrinidine are added, then 4.7 g (0.03) 3 mole of methyl iodide are added with stirring at room temperature and then mixes 45 in 3 hours. The resulting mixture is acidified, the precipitated 5-carbamoyl-4,6-dihydroxy-2-methylthiopyrimidine is filtered off and recrystallized from dioxane. This gives 1 g (16.6% of theory) of melting product at 360 ° C. EXAMPLE T. 5-cyano-2,4,6-trichloropyrimidine. • This compound is prepared from 5-carbamodlo-2,4,6-trihydroxypyrimidine, phosphorus oxychloride, by reactions at 100 ° C for 18 hours [see C. A. 62, 7775 (1965)]. The product recrystallized from gasoline with a boiling point of 100 ° -140 ° C, melts at 123 ° C, and the yield of the reaction is 65% of theoretical yield. 2-methylthiopyrimidine, phosphorus oxychloride and diethylaniline by boiling under reflux gives 5-cyan-4,6-di-Moro-2-methylthiopyrimidine, mp 107 ° C / from petrol / 15 93 115 16 Example U. 4,6-dihydroxy-5-methyl-2-methylthiopyrimidine. This compound is prepared by stirring 4,6-dihydroxy-5-formyl-2-fciopyrimidine at 0 ° C for 4 hours at 0 ° C. methyl iodide in aqueous solution. The product melts at 250 ° C. and the yield is 97.8% of theory. Example 5 4,6-dichloro-5-dichloromethyl-2-methylthiopyrimidine. 121 g (0.58 mol) of 4,6-dihydroxy-5-formyl-2-dimethythiothiopyrimidine are treated carefully with 600 ml of phosphorus oxychloride and after the turbulent reaction has ceased, 80 µl of diethylaniline are added. The mixture is refluxed for 6 hours, then the excess phosphorus oxychloride is distilled off under reduced pressure, the residue is carefully treated with ice and extracted with chloroform. The extractor hood was rinsed with water, dried and evaporated to dryness under reduced pressure. The residue recrystallized from gasoline with the addition of activated carbon, yielding 70 g (43.3%) of theoretical yield (4,6-dichloro-5-). dichloromethyl-2-methylthiopyrimidine, melting point 66 ° C. Example W. 6-ethoxy-5-formymyl-2-methyl-tto-4- thiomortpholinopyrimidine. To a solution of 11.4 g (0.041 mole) 4.6 The sodium ethoxide solution obtained from 0.95 g (0.041 mol) of sodium and 50 ml of ethanol is added dropwise while stirring under ice-cooling of-dichloromethyl-2-methylthiopyrimidine-2-methylthiopyrimidine in 100 ml of ethanol. The mixture is then stirred for 1 hour, then added to water and the mixture is extracted with chloroform. Chloroform is evaporated from the extract, the residue is dissolved in dioxane and, while stirring and cooling, 31 g (0.3 mol) of thiomorpholine are added and the mixture is allowed to stand overnight at 20 ° C. The mixture is then diluted with water, extracted with chloroform, the extract is rinsed with water, dried and the chloroform is evaporated. The residue is purified by chromatography on a Merck silica gel column, 0.2-0.5 mm, eluting with a gasoline-ethyl acetate mixture: 1. The homogeneous fractions were evaporated to dryness and the residue was recrystallized from gasoline, yielding 5.6 g (45.6% of theoretical yield) of 6-etho'xy-1-phonyl-2-methylthio-4-thomorphoHnopyrimidine. Product analysis. Formula C12H17N4OgS2 »molecular weight 299.42. Calculated: 48.14% C, 5.72% H, 14.03% N. Found: 48.45% C, 5.82% H, 13.78% NW analogously, from 4,6-dichloro-5-dichloromethyl-2-methylthiopyrimidine, sodium ethoxide and 1-oxythiomorpholine, 6-ethoxy-5-formyl-2-methylthio-4- (1-oxydothiomorpholine) is obtained. - Amino / -pyrimidine, which is recrystallized from ethyl acetate with dioxane, melts at <RTI ID = 0.0> 0: </RTI>: Example X 5-carboethoxy-2,4-dihydroxy-pyrimidine. This compound is prepared from the ethoxymethyl ester of malonic acid and urea . The product melts at 241-243 ° C. The following compounds are prepared in an analogous manner: a) 5-carboethoxy-4-hydroxy-2-morpholinopyrimidine is produced from the ethoxymethylene ester of malonic acid and morpholinoguanidine. ¬ crystallized from ethanol melts at 164-166 ° C, b) 5-carboethoxy-4-hydroxy-2-thiomorpholinopyrimidine is obtained from ethoxymethylene malonic ester and thiomorpholinoguanidine, which, after recrystallization from ethanol, melts at 133 ° C. 165 ° C. Example Y. 5-canboethoxy-2-chloro-4-thio-morpholineprimidine. 4 g (0.018 mol) of S-carboethoxy-E4-dichloropyrimidine, obtained by the method of A. Dornów, G. 13 Petsch [Diebigs Ann. Chem. 588, 45-61 (1954)] is dissolved in 70 ml of ice-cold ethanol and treated with a solution of 4.1 g (0.036 mol) of thiomorpholine while stirring at 0 ° C. The resulting dense crystal mass is stirred for 15 minutes, then poured into 150 ml of water, the crystals are drained off and washed with water. Yields 4.8 g (92.3% theoretical) of (5-carboethoxy-2-chloro-4Hthiomo-rpholinopyrimdine, m.p. 7K) -170C. Product analysis. Formula C11H1 ^ ClN3OS, molecular weight 287.75 Calculated: 45.91% C, 4.90% H, 14 ^ 60% N Found: 46.10% C, 5.06% H, 14.66% NW the following compounds were prepared in an analogous manner: a / from 5-carboethoxy-2,4-dichloropyrimidine and 1,1-dioxydothiomorpholine, 5-carboethoxy-2-chloro-4- (14-dioxydot) iomorpholine / -pyrimidine is obtained mp 143-147 ° C (from gasoline with ethyl acetate), b) from 5-carboethoxy-2,4-dichloropyrimidine and 1-oxydothiomorpholine to give 5-cartoethoxy-2-chloro-4- (1-oxidothio). morpholine (pyrimidine, mp 123-126 ° C) from butanol with cyclohexane (and c) from 5-carboethoxy-2,4-dichloro-6-methylpdrimidine, prepared by a method analogous to that described by A. Dornów, G. PetsCh, Liebigs Ann. Chem. 588, 45 ^ 61 (1954) from 5-carboethoxy-2,4-dihydroxy-45 -6-methylpyrimidine and phosphorus oxychloride with phosphorus pentachloride [R. W. Lamon, J. Het. Chem. 6, 2611-264 (1969)], by reaction with 1,1-dioxydothiomorpholine, 54 Carboethoxy-2-chloro-4- (1,1-dioxydothiomortpholine) (J6-methylpyrimidine 50, mp 145-148 ° C) is obtained. . Example Z. 5 J-carboethoxy-4-chloro-2-morpho-Mnopyrimidine. 14.4 g (0.057 mole) of 5-carboxy-4-hydroxy-2-morpholinopyrimidine are added to a mixture of 100 ml of phosphorus oxychloride and phosphorus sodium chloride and boiled under reflux for 20 minutes. a clear solution is formed. Excess phosphorus oxychloride is distilled from this solution, the residue is treated carefully with ice-cold water and slightly alkalinized with sodium bicarbonate, then the crystals obtained are filtered off and the crystals obtained are recrystallized from ethanol, yielding 5-carboethoxy-4. cMoro-2-morpho! inopyrimidine, mp 79-60.5 ° C. 65 In an analogous manner, from S, arboethoxy-4-hydro-17 to 115 18 x-2-thiomorphoylmopyrimidine and -phosphorus oxychloride with phosphorus pentachloride, Sn-cartonethoxy-4-cMoro-2-thiomorphoMno: pyrimidine is prepared. mp 81-83 ° C (from ethanol). The method according to the invention is illustrated in the following examples. Example 1 6-Methyl-4-morpholine-5-nitro-2-piperazine-piperazine. ° C of a solution of 19.4 g (0.1 mol) of piperazine hexahydrate in 300 ml of a 1: 1 mixture of acetone and dioxane is added dropwise while stirring and cooling a solution of 2.6 g (0.01 mol) obtained from 2,4-dichloro. -6-methyl-5-nitrothrimidine and morpholine 2-cMoro-6-methyl-4-morpholine-5-nitropyrimidine (mp 127-1290 [deg.] C) in 100 ml of a 1: 1 mixture of acetone and dioxane . After about 1 hour, the solvents are distilled off under reduced pressure, the residue is mixed with about 100 ml of water, the precipitate is filtered off, washed with water and dried, giving 3.0 g (97% of theoretical yield) (6-methyl-). 4-morpholine-5-nitro-2-piperazinopyrimidine. After post-precipitation with 2N ammonium hydroxide from a solution in about 0.2N hydrochloric acid, the product melts at 143-145 ° C. Analysis: Formula C → HaoNgOg (308.3). Calculated: 50.65% C , 6.55% H, 27.21% N. Found: 50.70% C, 6.74% H, 27.55% N. Example II. 6-methyl-5-n-trro-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared in an analogous manner to that described in Example 1 from 2-cMoro-6-methyl--5-nitro-4-thiomorpholinopyrimidine (mp 106-108 ° C) and piperazine. The product recrystallized from ethyl acetate melts at 141 ° C to 143 ° C. Example III. 6-Methyl-5-nitro-'2'-piperazine-4- (1-oxidothiomorpholine) -pyrimdine. This compound is prepared analogously to example 1, with 2-chloro-6-methyl-5 -nitro-4- (1-oxydothiomorpholine) -pyrimidines (m.p. 1471-150 ° C.) and piperazine. The product melts at 17-16-178 ° C (from ethyl acetate). Example IV. 5-nitro-2-piperazine-4- (1-oxy-dotdomorpholine) -pyrimidine. This compound is produced. 2-chloro-5-nitro-4- (1-oxydothiomorpholdn) -pyrimidine (mp 155-157 ° C) and pdperazine. The product melts at 135— »145 ° C. Example V. 6-Ethyl-4-imorpholine-5-nitro-2-piperazinopyrimidine. This compound is prepared analogously to that described in Example I, from 6-ethyl-2 -chloro-4-morpholine-5-nitropdrimidine (mp 87-88 ° C.) and piperazine. The product melts at 107 ° C <109 ° C. Example VI. 6-ethyl-5-nitro-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared in an analogous manner to that described in Example 1, from 6-ethyl-2-chloro-5-nitro-4-thomorpholinopH'imidine (mp 12-73 ° C.) and piperazine. The product melts at 111-113 ° C. Example VII. 6-ethyl-5-nitro-2-piperazine-4- (1-oxydothiomorpholdn) -pyrimidine. This compound is prepared analogously to that described in example 1, from 6-ethyl-2-chloro 5-nitro-4- (1-oxydothiomorphol'ino) -pyrimidines (mp 137-138 ° C) and piperazine. The product melts at 176-178 ° C. Example VIII. 5-nitro-2-piperazine-6-propyl-4-thiomorpholdnopyrimidine. . This compound is prepared in an analogous manner to that described in Example 1 from 2-chloro-5-nitro-6-propyl-4-thiomorpholinopyrimidine having the consistency of a d-piperazine resin. The product melts at 140 ° -42 ° C. Example IX. 5-nitro-2-piperazine-6-propyl-4- (1-oxydothiomorpholine) pyramidine. This compound is prepared analogously to that described in Example 1, with 2-chloro-5-nitro 6-propyl-4- (1-oxydothiomorpholine) -pirimidine (m.p. 108-111 ° C.) and piperazine. The product melts at 208-210 ° C (from methanol). Example X 6-isopropyl-5-nitro-i2-piperazine-4- (1-oxidotdomorpholine) -pyrimidine. in Example 1, from 2-chloro-6-isopropyl-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine (m.p. 140-h142 ° C) and piperazine. The product melts at 175-178 ° C / from methanol /. Example XI. 6-tertiary-butyl-5-nitro-2-piperazine-4- (l-oxydothiomorpholine) -ptrrimidine. This compound is prepared in a manner analogous to that described in example 1, with 6-tertiary butyl- -2-chloro-5-nitro-4- (1-oxydothiomorpholine), pyrimidine, m.p. 155.degree. To 57.degree. C. / d piperazine. The product melts at 185 ° C to 100 ° C (from methanol). 2- (N-carphboethoxypiperazine / r 40 -6-methyl-5-nitro-Z1-oxy-sydothiomonfoline). -Pyrimidine. This compound is prepared in an analogous manner to that described in example I, with 2-chloro-6-methyl - -5-niitro-4- (1-oxidothiomoTfolino (H-pyrimidine) (m.p. 147-150 ° C) and 'N-carboethoxypiperazine. The product melts at 150 ° C. -152 ° C (from ethyl acetate). Example XIII. 2- (N-formylpdperazine / -6-methylj5-nitro-4- (l-oxydothiomorpholdno) -pyrinides-. 90 degrees. This compound is prepared analogously to that described in Example 1 from 2-chloro-6-methyl--5-nitro-4- (1-oxydothiomorpholine) -pyrimidine (mp 147-150 ° C) and N -formylpipeTa- 55ine. The product melts at 202-2104 ° C (from ethyl acetate). Example 14. 4- (N-formylpiperazine) -6-methyl-6-nitro-2- (1-oxydothiomorpholine) 4-pyrimidine. 60 The compound phen is prepared by a method analogous to that described in Example 1, from 2-chloro-4- (NH 2), rm1-yl-piperazine (-6-methyl-5-nitropiximidine) (m.p. 163-165 ° C.) and 1- oxydotk) - monfold. The product recrystallized from water melts at 155-158 ° C. 93 115 19 Example XV. 6-Methyl-5-nitro-4-piperazine-2- (1-oxydothiomorpholine) -pyrimidine. This compound is prepared from 4- (N-formylpiperazine) (6-methyl-5-nitro-2-) 1-Oxydothiomortfoline (pyrimidine) (mp 155-158 ° C.) by refluxing with sodium hydroxide in methanol for several hours. The product melts at a temperature of 1-7-180 ° C (from water). Example XVI. 5-ni-trio-2-piperazine-4- (l-otesydothiomorphqlin) (6-pyrimidinecarboxylic acid. Methyl ester). This ester is prepared in an analogous manner to that described in Example 1 from 2-chloro-acid methyl ester. 5-nitro-4- (1-olxydothiomorpholdno (-6-pyrimidine) -Tiboxylic acid (mp. (Mp) from 164-t-165 ° C) and piperazine. The product recrystallized from methanol melts as it decomposes <temperature 196-1 & 80C. Example XVII. 5-nitron-2-pyperazine-4- / l- acid ethyl ester <) ixydothiomorpholino / ^ 6L-pyrimidine cathaphoxylic acid. This compound is prepared analogously to that described in example 1.1 from the ethyl ester. 2-Chlloro-5-nitro-4- (1-oxydothiomorpholine) -6-pyrimidine carboxylic acid (mp 128-130 ° C) and piperazine. The product melts at 173 ° -175 ° C. -? Example XVIII. 5-Chloro-2-piperazine-4- (1-oxydothiomorpholine / -6-pyrimidine-carboxylic acid nitrile). To a solution of 19.4 g / 0.1 mol / piperazine hexahydrate in 100 ml of dioxane is slowly added, 8 g / 0.02 mole; 2,5-di-chloro-4- (l-oxydothiomor! foilino / -6H-pyrimidium! carboxylic acid) nitrile. mp 145-147 ° C., obtained from 2,4,5-trichloro-4-pyrimidine carboxylic acid nitrile and 1-oxydothiomorpholine. During the addition, the mixture warms slightly and a solution is rapidly produced. After a short standstill, the mixture is evaporated to near dryness under reduced pressure and the residue is mixed with about 100 ml of water. The faint yellowish precipitate is filtered off, rinsed with water and dried, yielding 6.4 g (94% theoretical yield) of -chloro-2-piperazine-4- (l-oxydothiomorpholine) -6-pyrimidine carboxylic acid nitrile. mp 203-205 ° C. The product recovered with ammonia from the solution in about 0.2 N hydrochloric acid melts at 206 ^ 208 ° C. Product analysis: Formula C13H17NdOSCl / 340.8/ Calculated: 45.81% C, 5.03% H , 9.41% S, 10.40% Cl. Found: 45.50% C, 5.04% H, 0 45% S, 10.60% Cl. Same compound is prepared from nitrile hydrochloride of acid 5 -chloro-2-piperazine-4-thiomorffolin-6H-pyrimidine-carlboxyl / melts. with: signs of decomposition at 297-299 ° C / by oxidation with sodium metaperiodate in an aqueous environment. * "'¦ • ¦ Example XIX. Nitrile of 5-cMoro-2 ^ piperazine-4-thiomorpholine ^ 6 ^ pyrimidine tiboxylic acid .- .., .... This compound is prepared analogously 40 43 50 55 60 to that described in Example 1, from 2,5-dichloro-4-thiomorpholine-6-pyrimidinecarboxylic acid nitrile (mp 126-127 ° C) and piperazine. The product melts at 137 ° -140 ° C. C. The hydrochloride of this nitrile is obtained by recrystallization of the nitrile from 0.1N hydrochloric acid, m.p. 2S97-h299 ° C (decomposition). 1.8 g (0.005 mole) of 2-ethylsilphonyl-5-chloro-nitrile is slowly added to a solution of 2 g (0.03 mole) of piperazine in 50 ml of dioxane. 4- (1,1-Dioxythiomorifolin) -6-pyrimidinecaribacyl xylic acid, mp 234-237 ° C, obtained from 2-ethylthio-5-chloro-4-thiomorpholine-6-pyrimidinocartoxylic acid nitrile by oxidation with permanganese potassium iate in dilute hydrochloric acid. After a short standstill, the solution is evaporated to almost dry in vacuo and the residue is stirred with about 50 ml of water, then the precipitate is filtered off, washed with water and dried. 1.4 g (78% of theory) of 5-chloro-nitrile are obtained. 2-piperazine-4- (l, l, dioxy-thymorpholine) -6-pyrimidinecarboxylic acid which, after recrystallization from a 9: 1 mixture of methanol with dioxane, melts at 235-237 ° C. Product analysis: Formula C13HirN602SOi (356.8). Calculated. : 43.76% C, 4/80% H, 23.55% N, 9.94% Cl, Found: 43.90% C, 4.83% H, (23.40% N, 10.00% Cl. Such a dead compound is also obtained from 2,5-dichloro-4- (1,1-dioxydothiomorpholine (-1,6-pyrimidinecarboxylic acid) nitrile (mp 198-199 ° C) by reaction with piperazine in the manner of analogous to that described in Example XVIII. Example XXI 5-Chloro-2-piperazine-4-thiomorthphoyino-6-pyrimidine-tocatbokylic acid nitrile hydrochloride 1.0 g (0.003 mol) 5-chloro-2-phe nitrile - noxy-4-tLomorpholin o-6-pyrimidinecarboxylic acid, m.p. 112-1140C, obtained from 2,5-dichloro-4-thiomorpholine-6-pyrimidine-carboxylic acid nitrile and sodium phenate in phenol, is heated together with 1.3 g / 0.015 mol. Piperazine in 50 ml of dioxane at a temperature of about 50 ° C for 4 hours, then it evaporates under reduced pressure to a small volume and the residue is mixed with about 40 ml of water, the separated precipitate is filtered off, washed with water and dry. 0/7 g of 5-chloro-2-piperazine-thiomorpholine-C-pyrimidino-carboxylic nitrile hydrochloride is obtained, which is 72% of theoretical yield. After recrystallization from 0.1 N hydrochloric acid, the product melts. with signs of decomposition at 2B7-299 ° C. Product analysis: Formula C13H17Ne9Cl. HCl (361.3). Calculated: 23.26% N, Found: 23.62% N. This product is analogously obtained from nifryl (2-ethylthio-6-chloro-4-thio-morpholine acid). By boiling under reflux with piperazine in dioxane for about 8 hours. Example XXII. 5-chloro-2-acid nitrile. -piperazine-4- (1-oxo) to thiomorpholine (-6-pyrimidinecarboxylic acid) 0.3 g (0.001 mol) of 5-chloro-4-phenoxy-2-piperazine-6-pyrimidinecarboxylic acid nitrile of mp 126-128 ° C obtained by reacting 2,5-dichloro-4-phenoxy-eH-pyrimidinecarboxylic acid nitrile with piperazine in a cooled mixture of acetone and dioxane 1: 1, it is heated with 2.4 g / 0.02 mole (1-olxythiethiomonfoline) at a temperature of about 140 ° C for 90 minutes, after which the obtained dark-colored alloy is mixed with a small amount of water and the resulting crude product is purified on silica gel. [mu] m, eluting with an 8: 1 mixture of methanol with concentrated ammonium hydroxide. The pure product is triturated with ammonia from a solution in 0.2 N hydrochloric acid to give 5-chloro-2-piperazine-4- (1-oxydothiomorpholine) 6-pyrimidine-carboxylic acid nitrile, m.p. C. Example XXIII. 5-Bromo-2-piperazine-4-thiomorpholine-6-pyrimidinecarlboxylic acid nitrile hydrochloride. This compound is prepared analogously to that described in Example XVIII from "bromo-5-chloro-4-thiomorpholine / 6H-pyrimidine carboxylic acid nitrile" mp 138 ° -142 ° C.) and pyridine. By dissolving this nitrile in acetone and acidifying it with an alcoholic solution of hydrochloric acid, the hydrochloride of this nitrile is obtained, which melts with decomposition at 245 ° -247 ° C. EXAMPLE XXIV Acid nitrile. 5-Phhoromo-2-piperazine-4- (1-oxydothiomortpholine) -6-p-trrimidine-carboxylic acid. This compound is prepared analogously to that described in Example 18 from -bromo-2-chloro-4- / 1- nitrile Oxydothiomorpholine (-6-pyrimidine carboxylic acid, m.p. -180-182 ° C) and piperazine The product recrystallized from acetone melts at 180 ° -185 ° C. Example XXV. 5-chloro-2-acid methyl ester pdperazine-4- / l-oxydothiomorpholino / -6- -pyrimidine carboxylic This ester is prepared in an analogous manner to that described in Example 18 from 2,5-di-Moro-4- (1-oxydothiomorpholine) -6-pyrimidinecarboxylic acid methyl ester (mp 140-142 ° C.) and piperazine. The product melts at 160 ° C 1 M ° C. Example XXVI. 5-Bromo-2-piperazine-4- (1-oxido, thiomorpholine) -6-pyrimidine-carlboxylic acid methyl ester. This compound is prepared analogously to that described in Example XVIII from 5-bromo acid methyl ester. 2-chloro-4- (1-oxydothiomorpholine) -6-pyrimidinecarboxylic acid (m.p. 166-168 ° C) and piperazine. The product melts at 160 ° -163 ° C. Example XXVII. 6-methyl-4- 22-piperazine-2- (1-oxydothiomorpholino) -5-p-trimidinecarlboxylic acid nitrile. 2f, 7 g i / k), 01 mol / 4-chloro-6-methyl acid nitrile <-2- (1-oxydothiomorpholine) -5-pyrimidinecarboxylic acid, mp 251-253 ° C, obtained by reacting 2,4-dichloro-6-methyl-5-pyrimidinecarboxylic acid nitrile and 1-oxido thiomortpholine in chilled acetone, mixed with a solution of 8.6 g (0.1 mole) of piperazine in 80 ml of dioxane and refluxed for 30 minutes, then most of the solvent was distilled off under reduced pressure. The residue is mixed with about 80 ml of water, a small amount of 8 N sodium hydroxide is added, whereby an initially greasy but quickly precipitated reaction product is released. The precipitate is filtered off, washed with water and dried to give the nitrile of 6-methyl-4-piperazine-2Vl-oxydothiomorpholin (-5-pyrimidinecarboxylic acid) 2.8 gv (87% of theory). After dissolution in about 0.2 N hydrochloric acid and recovery with 2 N sodium hydroxide and recrystallization from water, 1.9 g (59%) of theoretical yield (1), mp 215-216 °, are obtained. C Product analysis: Formula - CH 2 H 2 OS / 320.4/ Calculated: 52.48% C, 6.29% H, 26.23% N, 10.01% S, Found: 52.10% C , 6.26% H, 26.05% N, 10.01% S. Example XXVIII. 5-ChloroJ6-methyl-2, -piperazinib-4- (1-oxydothiomorpholine) -pyrimidine. This compound is prepared analogously to that described in Example XXVII from 2,5-dichloro-6-methyl-4-) 1-o'xydothiomorpholine (pyrimidine) (mp 125-130 ° C) and piperazine. The product melts at 163-165 ° C (from ethyl acetate). Example XXIX. 5-ibromo-6-methyl-4-morpholine-2-piperazinopyrimidine. This compound is prepared in an analogous manner to that described in Example XXVII, from 5H-bromo-2-chloro-6-methylD-4-morpholinopyrimidine) mp 98-100 ° C.) and piperazine. The product 45 melts at 86 ° C. <90 ° C Example XXX. 5-bromo-J6-methyl-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared analogously to (described in example XXVII, from 5-bromo-2- 50-chloro-6-methyl-4-thiomorpholinopyrimidine / temperature mp 1125-126 ° C) and piperazine. The product melts at 1111 ° C to 12 ° C. Example XXXI. 5-bromo-6-methyl-piperazinom (1-oxydothibmortpholine) -pyrimidine. analogous to that described in Example XXVII of 5-bromo-2-chloro-6-methyl-4- (1-oxydothiomaphthblino) -pyrimidines (m.p. 128-130 ° C (/ and piperazine. The product melts at 158-160 ° C. Eo. Example XXXII Nitrile of 6-methyl-2-piperazine-4-thiomorpholine-5-pyrimidinecarbio; xylic acid. 2.7 g (0.10 mol) 4-chloro-nitrile 2- (N-formylpiperazine) -6-methyl-5-pyrimidinecarboxylic acid, m.p. 102-194 ° C, caused by reactions of 2,4-dichloro-6-methyl-5-acid nitrile -pyrimidinecarboxylic acid from N-formylpiperazine in environments in acetone and with cooling, it is mixed with 2.1 g (0.02 mole) of thiomorpholine in 60 ml of dioxane and refluxed for about 1 hour, then the solvent is distilled off under reduced pressure and The residue with the addition of about 60 ml of dopropanol and in the presence of sodium hydroxide is brought back to the boil under a reflux condenser for 30 minutes. The solvent is then evaporated off under reduced pressure, the residue is dissolved in dilute hydrochloric acid and the 6-methylb-2-piperazine-4-thiomorpholine--5-pyrimidine parfoxy nitrile is eliminated with concentrated ammonium hydroxide. The product, recrystallized from a 1: 1 mixture of methanol and water, melts at 146 ° -148 ° C. 1.6 g of product are obtained, representing 53% of theoretical yield. , Product analysis: Formula -C2A4S / 304.4 / Calculated: 55.24% C, 6.62% H, 27.61% N, 10.54% S. Found: 55.35% C , 6.57% H, 27.43% N, 10.50% S. For clade XXXIII. 6-methyl-5-nitro-2-piperazine-4-yl, 1-dioxydrot, iomorpholine / -pyrimidine. 1.6 g (0.005 mol) solution cooled to about 5 ° C. Methyl 5-nitro-and 2-piperazine-4-thiomorpholinopyrimidine (mp. 141-143 ° C) in about 60 ml of 0.5N hydrochloric acid is slowly added dropwise, with cooling and stirring, a solution of 0.8% 0.005 mol / potassium permanganate in 310 ml of water, then stirred for 1 hour at a temperature of about 5 ° C., and then the separated manganese dioxide was removed with a sodium hydrogen chloride solution. Concentrated ammonium hydroxide is added to the resulting solution, the precipitated product is filtered off, washed with water and dried, yielding 1.4 g (79% of theory) (6-methyl-5-nitro-2-piperazine-4-). 1,1-DioxythiomorpholineZ-pyrimidines, mp 208-211 ° C. After the ammonia solution several times from a solution in 0.1N hydrochloric acid, the product melts at 21 ° C. <1 ^ 213 ° C. Product analysis. Formula ClsH2iNtf04S /356.4/ Calculated: 42.81% C, 5.66% H, 0.00% S. Found: 43.60% C, 5.74% H, 9.06% S.P r from y k l a d XXXIV. 5-acetyl-2-n-piperazine-4- (l -oxydothiomorpholine / pyrimidine). This compound is prepared analogously to that described in example I from 5-acetyl-2-chloro-4- (l-oxydothiomorifoline / -pyrimidine). Decomposition at 168 ° -69 ° C.) and piperazine. In order to isolate the pure product, the crude product is mixed with water, a small amount of undissolved substances is filtered off, sodium hydroxide is added to the filtrate and extracted with chloroform. The extract is dried, the solvent is distilled off and the residue is recrystallized from ethyl acetate to give a product with a melting point of 140 ° C to 145 ° C. 2-formylpiperazine-4-thio-morpholino-chloropyrimdine, • 1115 24 '125.1 g of 4-thiomorpholine-2,6-dichloropyrimidine, melting point 118.5-121.5 ° C is dissolved in 1.2 liter of dioxane, treat with a solution of 125.6 g of N-monoformylpiperazine in 0.1 liter of dioxane and boil it under reflux for 2 hours, then drain the precipitated N-monoformylpiperazine hydrochloride, dilute the filtrate with 2 liters of water and cool it in the bath ice. The precipitated white crystalline 2-formylpiperazine no-4-thio; morpholine-6-chloropyrimidine is filtered off, washed with a small amount of 50% of dioxane and dried at 100 ° C to give 146 g / 90% of theoretical yield. (a product that melts at 195 ° to 9 ° C and 80 ° C.). 2-piperazine-4-thiomorpholine-5-nitro-6-cyclohexylaminopyrimidine dihydrochloride. 3.0 g of 2-methylmercapto-4-thiomorpholine-5-nitro-6-cyclbhexylaminopyrimidine with a melting point of 145-146 ° C is mixed with 8.0 g of anhydrous piperazine and heated for 1 hour at 130 ° C, then the obtained melt is diluted with 510 ml of water, causing precipitation of a living product which crystallizes upon rubbing with acetone. This product is dissolved in acetone, filtered with the addition of activated carbon and acidified with ethereal hydrochloric acid to give a precipitate of 2-piperazine-4-thiomorpholine-5-nitro-6-cyclohexylamino-pyrimidine dihydrochloride. This yields 2.6 g of product (64.5% of theory) which melts with decomposition at 173 ° C. Example XXXVII. 2-I-formylpiperazine-4- (1-oxydothiomorpho'lin) -5-nitropyrimidyl-6-malonic acid diethyl ester. To a suspension of 1.44 g of sodium hydride in 20 ml of anhydrous dioxane is added dropwise while stirring a solution of 10 × 8 g in 12 ml. of dioxane, then a hot 4 ft solution of 5.84 g of 2-formylpiperazine-4- (1-oxydothiomorpholine) -5-nitro-6-chloropyrimidine in 95 ml of dioxane is added, whereby the sodium ester is immediately formed. 2-formylpiperazine-4- (i-oxydothiomorpholine) -5-nitropyrimidyl-6-45-malonic acid diethyl in the form of a red-orange mass. This salt is dissolved in 100 ml of petroleum ether, left to form a precipitate and filtered off, then dried, dissolved in 50 ml of water, neutralized with 2N hydrochloric acid and extracted with a 2: 1 mixture of chloroform and methanol. The extract was evaporated to give 6.9 g of 788.0% of theory (2-formyl-piperazine-4- (1-oxydothiomorifolin) -5-nitropyrimide-HS-malonic acid diethyl ester as a yellow resin product. tinted. Testing by thin-layer chromatography on a silica gel plate using a 75: 25: 1 mixture of benzene with ethanol and concentrated ammonium hydroxide as eluent shows that product 60 is homogeneous, Rf = 0.55. . 2 -Piperazine-2-Zil-oxydothiomorpholine (1 S-nitropyrimyl-6-acetic acid, ethyl ester) 65 5.8 g of sodium are dissolved in 100 ml of anhydrous ethanol, 4.35 g of acid diethyl ester are added 93 115 26 Su 2-formylpiperazine-4- (1-oxidothiomorphino) -5-nitropyrimidyl-6-malonic (see example XXXVIrI) and the dark red solution is boiled under reflux for 1.5 hours and then distilled off ethanol, the residue is mixed with ice water and extracted with ethyl acetate. The solvent was evaporated from the extract to give β2-piperazine-4- (1-oxyothiomorpholine) -5-nitropyrimidyl] -6-acetic acid ethyl ester as a resin residue in an amount of 1.2 g (34% in theory). Examination of thin layer chromatography on a silica gel plate using a 75: 25: 1 mixture of benzene, ethanol and concentrated ammonium hydroxide as eluent shows that the product is homogeneous, Rf = 0.4. Example XXXIX. Hydrochloride. 2-piperazine-4- (1-oxydothio-morpholine-Z-S-nitropyrimidyl-e-malonic acid diethyl ester). 2.95 g of 2-formyl-piperazo-2 -Z1-oxydothiomortpholine (N-tropyrimidyl-6-malonic acid diethyl ester) are dissolved in a mixture of 75 ml of ethanol with 75 ml of saturated ethanolic hydrochloric acid and allowed to stand at room temperature. for 24 hours, then the solvent is distilled off at room temperature under reduced pressure and the crystalline residue is crystallized from ethanol. 1.57 g (52.3%) of theoretical product are obtained, which melts with decomposition symptoms above 335 ° C. The thin layer chromatography method as described in Example XXXVIII shows that the hydrochloride obtained is a homogeneous product, iRf = 0.25. Product analysis: Formula C19H29CINSO07 (521.00). Calculated: 43.80% C, 5.01. % H, 16.13% N, 6.81% Cl. Found: 43.80% C, 5.69% H *, 15.87% N, 6.97% Cl. Example XL. 2-Formylpiperazine-4- / 1-ox-thymorpholin Z-S-nitro-e-methylmercaptopyrimidine. 0.27 g of metallic sodium was dissolved in 15 ml of ethanol and the solution was saturated with methyl mercaptan by bubbling nitrogen through the vessel as a protective gas. Then, a solution of 2-formylpdpyrazine-4- (1-oxydothiomorpholine) (5-nitro-6-chloropyrimidine) in a mixture of 20 ml of ethanol and 20 ml of dioxane, heated to about 80 ° C, is immediately poured into the solution *. a precipitate of sodium chloride is immediately formed. To complete the reaction, stirring was carried out for 1 hour more, then the solvent was distilled off, the residue was mixed with water and extracted three times with chloroform. The extract is dried over sodium sulphate, the chloroform is evaporated off and the sticky yellow residue crystallizes in ethyl acetate. The yield is 2.5 g (82.5% of theory) of 2-formylpiperazine-4- (1-oxydothiomorpholine) -5-nitro-6-methyl mercaptopyrimidine, mp 238 ° C. Example XLI. 2-piperazine-4- (1-oxydothiomorpholino); - 5-nitro-6-meltylomerlcaptopyrimidine. 1.8, g 2-formylpiperazine-4- (1-oxydothiomorpholin / -i5-nnro-6-methylmercaptopyrimidine). mp 168-173 ° C. and 50 ml of 2 N hydrochloric acid are heated on a steam bath for 45 minutes, then cooled to room temperature, treated until saturated with anhydrous potassium carbonate and extracted with chloroform. The extract was dried over potassium carbonate, the solvent was distilled off and the residue was recrystallized from ethanol to give 0.6 g (36.1% of theory) of "2-piperazine-4- (1-oxydothiomortholino) -15-nitro. - -6-methyl mercaptopyrimidine, melting point 230 ° C. Example XLII. 2-foTmylpiperazine-4- / l-oxydothiomorpholine / -5-nitro-6-ethyl mercaptopyrimine. This compound is prepared analogously to that described in example XL from 2-formylpipe- zine-4-and / l-oxydothiomorpholine / -5-naltro-6-chloro-pyrimidines (mp. 176-178 ° C) and ethyl mercaptan. The product melts at 168-173 ° C and the yield is 63% of theory. Example XLIII. 2-: piperazine-4- / 1-oxydothiomo rfolino / -5-nitro-6-ethyro, mercaptopyrimide. Na. This compound is prepared in a manner analogous to that of Example XLI, from 2-formyl piperase-4. - (1-Oxydothiomorpholine) N-5-nitro-6-ethylmercaptopyrimidine and 2N hydrochloric acid. The product melts at 225 ° -28 ° C, the yield is 67% of theory. Example XLIV. 2-formylpiperazine-4- / l-oxydothioimorpholiino / -5-nitro-6-mercaptopyrimdine. This compound is prepared in a manner analogous to that described in example XL, from i2-formylpiphenosine-4- / l-oxydothiomorpholine / -5-niltro -6-c, hloroT. pyrimidines, mp 176-178 ° C and hydrogen sulfide. The product melts with decay symptoms above 240 ° C and the yield is 87% of theory. Example XLV. 2-formylpiperazine-4- (1-40-oxydothiomorpholino) -5-nitro-6-n-propylomerl capto-pyrimidine. 1.9 g of 2-formylpaperazine-4- / 1-oxidothiomorpholin Z-S-nitro-e-marktopyrimidine, melting with symptoms, decomposition at 24 ° C, dissolved in 30 ml of methanol and treated with 0.7 g potassium methoxide, then 1.2 g of n-propyl bromide are added and the mixture is stirred at room temperature for 5 hours. Then it is diluted with 100 ml of water and extracted with chloroform. The extract is dried over sodium sulfate and evaporated to give a sticky residue which does not crystallize. 1.5 g (71% of theory) of (2-formyl-piperazine-4-) 1-o-xydoltiomorpholine / -5-nitro-6-n-propyl mercaptopyrimidine are obtained. Example XLVI. 2-piperazine-4- (1-oxydothiomorpholine) -5-nitro-6-n-propyl mercaptopyrimide. This compound is prepared in an analogous manner to that described in Example XLI, from 2-formyl piperase-4- / 1 -oixydothiomorpholino (-5-natro-6-n-propyl mercapto pyrimidine and 2N hydrochloric acid). The product melts at 147-150 ° C., the yield is 62% of theory. Example XLVII. 2-formylpiperazine-4- (1-oxydothiomorpholine / -6-nitro-6-allylmercaptopyrimine. 27 93 115 28) This compound is prepared in a manner analogous to that described in Example XLV from 2-formylpyrazine-4- / 1-oxydothio-morpholino / -5-nitro-6-mercaptopyrimidine and allyl bromide. The product is obtained in the form of a non-crystallizing, viscous resin in a yield of 94% theoretical. Example XLVIII. 2-piperazine-4- / 1-oxy-do-thiomorpholino / -5-n-trro-6-allyl O'-mercaptopyrimidine. This compound is prepared in a manner analogous to that described in example XLI, from 2-formylpiphen-4- / 1- oxydoithiomorpholino / -5-n-trro-! 6-allyl-mercaptopyrimidine and 2 N hydrochloric acid. The product melts at 139 ° C and the yield is 45% of theoretical. Example XLIX. 2-formylpiperazine-4- (1-oxydothio, morpholino) -15-nitro-6-cyclohexylamino-pyrimidine. 7.78 g of 2-formylpiperazine-4- (1-oxydothiomorpholine) -5-riitro-6-cMoropyrimidine, mp 176-178 ° C, are dissolved in 150 ml of dioxane, 4.35 g of cyclohexylamine are added and kept there. it is boiled for 1.5 hours, then cooled, diluted with 200 ml of water and extracted with 3 portions of 50 ml of chloroform each. The extract is dried over sodium sulphate, filtered with the addition of activated carbon, evaporated and the residue recrystallized with 150 ml of ethanol. 7.6 g (84.5% of theoretical yield) (2-formylpipierazine-4- (1-oxidothiomorpholine) -5-: nitro-6-chloropyrimidine with a melting point of 254 ° -257 ° C are obtained. Example L. 2-Piperazine-4- (1-Oxydothio-morpholine / -5-nitro-6-cyclohekylamino-pyrimidine monohydrochloride). y 1.0 g of 2-formylpiperazine-4- (1-oxydothiomorpholin) -5-nitro-6-cyclohexylaminopyrimidine, melting point 254-257 ° C and 30 ml of 2N hydrochloric acid are heated on a steam bath in the course of 1.5 hours, then the filtrate is evaporated to dryness The residue is recrystallized from ethanol to give 0.7 g (67% of theory) of product which melts with decomposition at 273 ° 275 °. 2-formylpiperazine-4- / 1-oxy-thymorpholine This compound is prepared analogously to that described in example XLIX from 2-formylpyrazine-4- / 1-oxidothiomorpholine / -5-niltro-6-chloro-pyrimidine with mp 176-176 ° C and aniline. The product melts at 200-2404 ° C and the yield is 73.2% of theoretical. -.nitro-6-enylaminopyrinidine * This compound is prepared from 2-formylpiperazine-4- (1-oxydothiomorphino) -5-nitro-6-phenylaminopyrimidine and 2N hydrochloric acid. It dies at 235 ° C and the yield is 46.4% of the theoretical value. Example LIII. 2-formylpiperazine-4- (l-oxydo, thiomorpholine / -5-nitro-i6- (4-chlorophenylamine) -pyrimidine. This compound is prepared in a manner analogous to that described in example XLIX by the reaction of 2-formylpiperazine 4 (1-oxydothiomyifolin) -5-nitro-6-chloropyrimidine, mp 176-178 ° C. from 4-chloroaniline. The product melts at 248 ° C, the yield is 72.9% of theory. Example LIV. 2-piperazine-4 ^ / 1-oxydothio, morpholine (-5-nitro-16- (4-chlorophenylamino) -pyrimidine monochloride. This compound is prepared analogously to that described in example L, from 2-formylpiper - zino-4- (1-oxydothiomorpholdrio) -5-nitro-6- (4-chlorophenylamino) -pyrimidine and 2N hydrochloric acid. The product melts with decomposition at 300 ° C. The yield is 53.2% of the theoretical value. Example LV. 2-Formylpiperazine-4- (1-oxy-thymorpholine) -5-nitro-6- (2-caiiboxy [Phenylamino] -pyrimidine. This compound is prepared in an analogous manner to that described in Example XLIX by Reactions 2 -formylpiperazine-4-l-oxydothioimorpholine - -5-nitro-6-chloropyrimidine, mp 176-178 ° C. with anthranilic acid in the presence of three times the molar ratio of triethylamine. The product melts with decomposition at 163-168 ° C, the yield is 63% of theory. Example LVI. 2-piperazine-4- (1-oxydothiomorpholine) -5-nitro-6- (2-carboxyphenyl-amino) -pyrimidine monochloride. This compound is prepared in a manner analogous to that described in example L, from 2-formylpiperazine-4-) 1-oxy tiomorpholane (-5-nitro-6- (2-carboxyphenylamino) -pyrimidine and 2N hydrochloric acid solution. The product melts at 290 ° C and the yield is 73.4% of theory. Example LVII. 2-piperazine-4- (1-oixydothio! Mortfoliino) -5-nitro-6- (2-carbomethoxyphenylamino) -pyrinidine dihydrochloride. This compound is prepared. in a manner analogous to that described in Example XXXIX, by refluxing for 3 hours 2-formylpiperazine-4n (1-oxydothiomorpholine) -5-nitro-6- (2-carboxyphenylamino) - -pyrimidine with methanolic hydrochloric acid solution. The product melts with decomposition at 210 ° C to a yield of 53.5% of theoretical. Example LVIII. 2-formylpiperazine-4- (l-oxydothiomorpholiino) -5-nitro-6- (2-pyridylamino) -50-pyrimidine. This compound is prepared in a manner analogous to that described in example XLIX from 2-formylpyrazine-4 - (1-Oxydothiomorpholine) -5-ntro-6-chloropyridine, mp 176-178 ° C and 2-aminopyridine. The product melts at 240-243 ° C and the yield is 52% of theory. Example LIX. 2-piperazine-4- / lo! Pesydothiomorpholine / -5-niitro-6- / 2-pyridine-60-amino-7-pyrimidine dihydrochloride. This compound is prepared analogously to that described in Example XXXIX, with '2-formyl- piperazine-4- (1-oxydothiomorpho'lino) -5-nitro-6- (2-pyridylamino-Z-pyrimidine) and hydrochloric acid methanol. The product melts with decomposition at 237.5-240 ° C, the yield is 73% of theory. Example LX. 2-formyl-piperazine-4- / 1-o'xy-dotiomo; r 1 -folno / -5-nitro-i6- / 4-pyridylqamino / -pyrimidine. This compound is prepared. in a manner analogous to that described in example XLIX, with 2-formylpyrazine-4- (1-oxydithiiorpholine / -i5-nitro-6-ch, loropyrimidine and 4-aminopyridine). The product melts at 240-243 ° C theoretical. Example LXI. 2-piperazine-4- (1-oxydothio'morpholine) -l5-nitro-6- (4-pyridylamino) -pyrimidine dichlohydride. This compound is prepared analogously to that described in Example XXXIX, from 2 -formyl-piperazine-4- (1-oxydothiomorpholine) -5-nitro-6- (4-pyridylamino) -pyrimidine and methanolic hydrochloric acid. The product melts with signs of decomposition at 335 ° C and the yield is 81.8% of theory. Example LXII. 2-piperazine-4- (1,1-dioxy-thymorpholine) -5-nitro-6-cyclohexylaminopyrimidine. For a solution cooled to 10 ° C, 68 g, 2-piperazine-4- (1-diolxydothiomorpholine) -5 - -nitro-6-cyclohexylaminopyrimidine in 100 ml of 2N sulfuric acid, a solution of 0.316 g of potassium permanganate in 20 ml of 2N sulfuric acid is added dropwise within 15 minutes, then left for 3 hours at 10 ° C and then the separated crystals are filtered off The product is mixed with 30 ml of water, an excess of concentrated ammonium hydroxide is added to the suspension obtained and the mixture is extracted with chloroform. The extract was evaporated and the residue was recrystallized from ethanol to give 0.25 g (19% of theoretical yield) of 2-piperazine-4- (1,1-dioxydothiomorpholine) -5-nitro-6-cyclohexylaminopyrimidine, melting point 214-216 ° C. Example LXIII. 5-carboethoxy-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared in an analogous manner to that described in example LXVI from 2-chloro-5-carboethoxy-4-thiomorpholine-pyrimidine, m.p. 70-71 ° C with piperazine in dioxane (2 hours, 1'00 ° C). The yield is 17.5% of theory and the product melts at 115 ° C. (from gasoline with benzene). Example LXIV. 2-piperazine-4- / l-oxy-do-thiomorpholine / -5-fluoropyrimidine. This compound is prepared analogously to that described in example LXVI, boiling in dioxane for 2 hours. -i / 'l-oxydothio, morpholino / -5-fluoropyrimidines from piperazine. The yield is 64% of theory and the product converted to the dihydrochloride hemihydrate melts at 203-205 ° C (from ethanol diluted with water). Class d LXV. 6-ethoxy-5-nitro-2- (1-olxy-thymorpho'ldno) -4H-piperazinopyrimidine. This compound is prepared by treatment with hydrogen peroxide at 20 ° C for 1 hour on 6-ethoxy-5-nitrile: ro-4 -piperazine-2-thiomorpholinopyrimidine, mp 84- ^ 86 ° C. The product recrystallized from isopropanol with petroleum ether melts at 108-110 ° C. Example LXVI. 6-ethoxy-5-nitro-2-piperazine-4-thiomorpholinopyrimidine. To 68 g (0.8 mol / piperazine melt) 23 g / 0.07 mol / 6-ethoxy-2-methylthio-5-nitro are added. The -4-thiomorthpholinopyrimidine is heated for 1 hour at r10 ° C., then cooled, and ice water is added to the mixture. The yellow precipitate obtained is filtered off, washed with water and recrystallized from isopropanol to give 18 g (70% of theory) of 6-ethoxy-5-nitro-2-piperazine-4-thiomorpholinopyrimidine, melting point 66.5 —168.5 ° C. Product analysis: Formula C14H22Np3S /354.3/ Calculated: 47.44% C, 6.26% H, 0.05% S. Found: 47.50% C, 6.23% H, 9.02% S. Example LXVII. 6-ethoxy-5-nitro-4- (1-oxy-thio-thio-morpholine / -2-piperazinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-ethoxy-2-methylthio-5-nitro (1-Oxydothiornorpholine) -pyrimidine from piperazine within 20 minutes. The product recrystallized from ethanol melts at 2 & 3-224 ° C. Example LXVIII. 6-allyloxy-5-nitro-2-piperazine-4-thiomorpholinopyimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-a, 11yloxy-2H-methylthio-5-nitro-4-thiomorpholinopyridine from piperazine within 15 minutes at 120 ° C. the free base product melts from 0.5 mole of water of crystallization at 132 ° -133 ° C. (from carbon tetrachloride with gasoline). Example LXIX. 6-allyloxy-4n / 1,1-dioxy-thymorpholine / -5-nitro-2-n-piperazinopyrimidine. This compound is prepared in a manner analogous to that described in Example LXVI by the reaction of 40 e-allyloxy ^ -Al-dio ^ ydothiomorpholine / ^ - methylthio-5-nitropyrimidine with piperazine at 120 ° C. for 4 minutes. The product melts at 143-147 ° C (from isopropanol). Example LXX. 6-n ^ propbxy-4- / 1,1-di-oxydothiomorpholine / -5-nitro-2-piperazinopyrimidine. This compound is prepared in a manner analogous to that described in Example LXVI by 6-n- pro: poxy-4-vfl4-dioxydothio | morpholino -, 2-methylthio-5-nitropyrimidine from piperazine at 120 ° C. for 20 minutes. The product recrystallized from carbon tetrachloride melts at 166 ° C to 169 ° C. Example LXXI. 6-n-propoxy-5-nitro-4- (1- 55-oxydothiomortholino / J2 -piperazinopyrimidine. ^ This compound is prepared in a manner analogous to that described in Example LXVI, by the reaction of en- propoxy- ^ -methylthiio ^ -Zl- oxydothiomorpholine / -5-nitropyrimidine with piperazine at 60-120 ° C for 20 minutes. The product, recrystallized from aqueous ethanol, melts at 170.5 ° -72.5 ° C. Example LXXII. 4- (1,1-dioxydothiomorpholine) N-5-nitro-2-piperazine-6-isopropoxypyrimidine. 65 This compound is prepared in a manner analogous to that described in Example LXVI by reacting 4- (1, 1, -dioxydothiomorpholine) -methylthio-S-nitro-6-isopropoxypyrimidine with piperazine at 12 ° C during 20 minutes. The product recrystallized from ethanol melts at 2 (UM2B, 5 ° C. Example LXXIII. 6-n-4utoxy-5-nitro-4- (1-4 oxydothiomorpholine) -2-piperazinopyrimidine. This compound is prepared in a manner analogous to that described in the example. LXVI, by reaction of 6-nH-butaxyJ2-methylthio-5-nitro-4- ^ 1-oxydothioanorpholin / -pyrimidine with piperazine at 130 ° C for 15 minutes The product converted to the hydrochloride and recrystallized from ether with acetone melts. with signs of decomposition at 1 60 ° C 62 ° C. Example LXXIV. 6-neopentyloxy-5-nitro -2-piperazine-4-thiomorpholdnopyrimidine. This compound is prepared and prepared in a manner analogous to that described in Example LXVI by reaction of 2-methylthio-6-neoipentyloxy-5-nitro-4-thiomorpholinopyrimidine with piperazine at 130 ° C. for 30 minutes. LXXV. 5-nitro-2-piperazine-6-isopropoxy-4-thiomorpholinopyrimidine. This compound is prepared by an analytical method. based on that described in Example LXVI, by reacting 2-methylthio-5-nitro-6-isopropoxy-4-thiomorifolinopyrimidine with piperazine at 130 ° C. for 15 minutes. The product recrystallized from isopropanol melts at 137.5-140 ° C. Example LXXVI. 5-nitro-4- (1-oxydothiomorpholine) -2-piperazine-6-isopropoxypyrimidine. This compound is prepared "analogously to that described in Example LXXVI by reacting 6-isopropoxypyrimidine with piperazine at 130 ° C." in 15 minutes The product crystallized from isopropanol melts at 204.5-206 ° C. Example LXXVII. 6-n-butoxy-4- (1,1-di-oxydothiomorpholine) -5-nitro 2-piperazinopyrimidine. This compound is prepared in a manner analogous to that described in Example LXVI by reacting 6-n-butoxy-4- (yl-d -Wofxydothiomorpholine) -2-methylthio-5-nitropyrimidine with piperazine at a temperature of 1 '. 30 ° C. in 15 minutes The product, recrystallized from aqueous ethanol, melts at 18.1-183 ° C. - Example LXXVIII. 6-n-butoxy-5-nitro-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-n-butoxy-2-methylthio-5-nitro-4-thiomorpholinopyrimidine with piperazine at 130 ° C. C within 10 minutes. The product recrystallized from isopropanol melts at 1.17 µmol. ° C. Example LXXIX. 6-n-ibutoxy-4-morpholine--5-nitro-2-ipiperazinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-n-tutoxyT-2-methylthio-4-morpholine-5- nitropyrimftidine with piperazine within 16 minutes at 120 ° C. The product recrystallized from hydrated methanol melts at 63-65 ° C. Example LXXX. 4-morifolino-5-nitro-2-pipazine-6-isopropoxyxia irmiidine. This compound is prepared analogously to that described in example LXVI by reacting 2-methylthio-4-imorpholine-5-nitro-6-isopropoxypyr. - midines with piperazine within 10 minutes at 130 ° C. The product recrystallized from isopropanol melts at 117 ° -119 ° C. io Example LXXXI. 6-II-rzeddbutoxy-5-niitro-2-piperazine-4-thiomorpholinopyrimidine. This compound is prepared in a manner analogous to that described in Example LXVI by the reaction of 6-II-order ibutO'xy-2-methylthio-5- nitro-4-thiomorpholinopyrimidine with piperazine at 130 ° C for 20 minutes. The product, recrystallized from gasoline, melts at 123 ° -126 ° C. Example LXXXII. 6-II-order-butoxyH5-nitro -4- (1-oxydothiomortpholine / -2-piperazinopyrimidine. This compound is prepared in a manner analogous to that described in example LXVI by the reaction of 6-II-order butoxy-2-methylthio-5). nitro-4- (1-oxydothiomorpholine) pyrimidine with piperazine at 130 ° C. for 20 minutes. The product recrystallized from gasoline with carbon tetrachloride melts at 156 ° -158 ° C. / Example LXXXIII. 6-II-order butoxy-4- / 1,1-dioxydothiomorpholine / -5-nitro-2-piperazinopyridine. This compound is prepared in a manner analogous to that described in example LXVI by the 6-II-order butoxy- 4- (11,1-dioxydothiomorpholine) -2-methylthio-5-nitropyrimidine with piperazine at 130 ° C. for 20 minutes. The product recrystallized from carbon tetrachloride melts at 1-3 ° -104.5 ° C. Example LXXXIV. 6-ethoxy-4- (1,1-dioxy- to thiomorpholine / -5-nitro-2-piperazinopyrinlidine. This compound is prepared analogously to that described in example LXXI by the reaction of 6-ethoxy-4- / l, 1-Dioxydothiomorpholine / -2-methylthio--5-nitroipyrimidine with piperazine at 120 ° C for 20 minutes. The product which crystallizes from 0.5 mole of water of crystallization melts at 190-193 ° C (from carbon tetrachloride). Example LXXXV. 4-morpholino-5-nitro-2-piperazine-6-n-propoxypyrimidine. This compound is prepared "analogously to that described in example LXVI, by reacting 50 2-methylthio-4-mo, rfolin-5- nitro-6-n-propbxypyrimine with piperazine at 120 ° C in minutes The product recrystallized from gasoline melts at 10.1-104 ° C. Example LXXXVI. 5-nitro-2-piperazine-6- 55. -n -propoxy-4-thiomorpholinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 2-methylthio-5-nitro-6-n-propoxy-4-thiomorpholine-pyrimidine with piperazine at 120 ° C and 60 ° C. 20 minutes The product recrystallized from petrol melts at 92-95 ° C. Example LXXXVII. 6-ethoxy-5-cyano-4- (1,1-dioxydothiomorpholine) -2-piperazinopyrimidine. This is prepared in a manner analogous to that described in Example LXVI by the reaction of 6-ethoxy-5-cyano-2-methylthio -1,1-dioxydothiomorpholine Z-pyrimidine with a melting point of 194 ° C with piperazine at 130 ° C for minutes. The product recrystallized from ethanol melts at 235 ° C. Example LXXXVIII. 6-ethoxy-5-cyano-4-morpholine-2-piperazinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-ethoxy-5-cyano-2f-methylO'tio-4-morpholmopyrim- dyes, mp 104 ° C with piperazine at 120 ° C in 30 minutes. The hydrochloride of this compound melts at 239 ° C. (from ethanol). Example LXXXIX. 6-ethoxy-5-cyano-2-pipazine-4-thiomorifblinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-ethoxy-5-cyano-2-methylthio-4-thio, morpholinopdrimidine, mp 157-159 ° C. from pyramidine. These reactions are carried out at 130 ° C for 30 minutes. The product recrystallized from i-gasoline melts at 119 ° C. Example XC. 5-cyano-6-methoxy-4- (1-oxy-thymorpholine) -2-piperazinopyrimidine. This compound is prepared analogously to that described in Example LXVI, by reacting 5-cyano-6-methoxy-2 -methylthio-4- (1-oxydothiomorpholineZ-pyrimidine, m.p. 184-186 ° C from piperazine. The reactions are carried out for 30 minutes at 130 ° C. The product, recrystallized from water, melts with decomposition at 270 ° C. Example XCI. 5-cyano-4- (l-oxydothiomorphoMna / -2-ipetazine-6-n-propoxypyrimidine. This compound is prepared in a manner analogous to that described in example LXVI by the reaction of -cyano-2-methylthio-4-) 1-oxidothiomorifoline / -6-n-propoxypyrimidine, mp 190-192 ° C from piperazine. The reactions were carried out at 130 ° C for 1.5 hours. The product, recrystallized from water, melts at 177 ° -179 ° C. * Example XCII. 5-Cyano-4-morpholino-2-piperazine-6-n-propoxypyrimidine. This compound is prepared analogously to that described in Example LXVI by the 5-cyano-2-methylthio-4H-morpholine-6-n reaction. -propoxypyrimidine, m.p. 107 ° C from piperazine. The reactions were carried out at 130 ° C for 1.5 hours. The hydrochloride of this compound decomposes above 230 ° C. Example XCIII. 5-cyano-2-piperazine-6-n-propoxy-4-thiomorpholinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting -cyano-2-methylthio-6-n-propoxy-4-thiomorpholine-pyrimidine mp 120-122 ° C. with piperazine at 130 ° C. for 1 hour. The hydrochloride of this compound, recrystallized from ethanol, melts at 248 ° C. EXAMPLE 14CIV. 6-ethoxy-5-cyano-4- (1-oxy-thymo-tpholino) u2-piperazinopyrimidinal 44 This compound is prepared analogously to that described in Example LXVI by the 6-ethoxy-5-cyano-2-methylthio reaction. -4- (1-Oxydothio-morpholine) -pyrimidines, m.p. 190 ° C from piperazine. The reactions were carried out at 120 ° C. for 1 hour. The product crystallizes from 0.5 mole of water and, recrystallized from water, melts at 205 ° C. Example XCV. 6-ethoxy-5-, formyl-2-pip- and timesno-4-thiomorpholinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-ethoxy-5-formyl-2-methylthio-4-thiomorpholinopyrimidine. with a melting point of 101 ° C with a pipeline. The reaction at 130.degree. C. takes 1 hour. The product recrystallized from gasoline melts at 110-1,113 ° C. Example XCVI. 6-ethoxy-5-formyl-4- (1- -o'xydothiomorph; lino / -2-piperazinopyrimidine. This compound is prepared analogously to that described in example LXVI by reacting 6-ethoxy-5-formyl-2-methylthio). 4- (1-oxydothiomorpholin) -pyrimidines, m.p. 163 ° C from piperazine. These reactions are carried out at 140 ° C for 1 hour. The product crystallized from ethyl acetate melts at 180 ° C. EXAMPLE XCVII. 6-ethoxy-5-nitro-4- (1-oxy-thymorpholine) -J2-piperazinopyrimidine. 52 g (0.6 moles) of piperazine are dissolved in 120 ml of boiling dioxane and 61.5 g (0.18 mole) of 6-ethoxy-2-methylthio-5-nitro are added to the solution over 30 minutes. -4- (1-oxydothiomorpholine) -pyrimidines, the mixture is then boiled under reflux for 45 minutes and then poured into 1.5 liters of ice water, the yellow precipitate is filtered off ¬ was washed with water and recrystallized from ethanol. The yield is 46.1 g (65.8%) of theoretical yield 40 6-ethoxy-5-nitro-4- (1-oxidothiomorpho) -piper * - zinopyrimidine, mp 222— - 2f23 ° C. Example XCVIII. 5-Cyano-6-methoxy-2-piperazine-4-thiomorpholinopyrimidine. 45 This compound is prepared in an analogous manner to that described in Example XCIV by reacting 5-cyano-6-methoxy-α-methylthio-4-thiomorphol nopyrimidines, m.p. 134 ° C. with piperazine in dioxane at 100 ° C. for 8 hours. The hydrochloride of this compound, crystallized from ethanol, melts with symptoms of decomposition at a temperature of +8 ° C. Example XCIX. 6-ethoxy-5-nitro-4- (1-oxy-thiomoifolm-7-2-piperazin-pyrimidine). 55 50 g / 0.15 mol / 6-eftoxy-2-methyltho-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine and 64.6 g / 0.15 mol / piperazine are dissolved in 150 ml of diethyl sulfoxide and stirred at room temperature for 6 hours, then poured into ice water, the crystalline product was filtered off, washed with water and recrystallized from ethanol. 39.3 g (70.7% of the theoretical yield) (e-ethoxy-nitro-1-oxidothiomorpholine) -2-p-perazinopyrimidine with a melting point of 222-223 ° C are obtained. 65 By treating an ethanolic solution of the base obtained with an equivalent amount of the corresponding acid, the following salts of the base are obtained, for example: thymate, C18H2ffH clade at a temperature of 180-185 ° C. C, p-toluenesulphonate, C21H30N607S2, melts at 133-137 ° C (with a small amount of methanol) and succinate, C16H2sNd06S, melts with decomposition at 194-196 ° C (from methanol). 6-.methoxy-5-nitro-4- (1-oxido-thiomorpholinoy-2-piperazinopyrimidine. This compound is prepared analogously to that described in example XCVIII by reacting 6-methoxy-2-methylthio-5-ndtro-4). - (1-Oxydothiomorpholin) -pyrimidine from piperazine in dimethylsulfoxide for 4 hours at 20 ° C. The product recrystallized from dopropanol melts at 11-17-5 ° C. 6-ethoxy-5-nitro-4- (1-oxydothiomorpholine) -2-piperazinopyrimidine. 12 g 70.037 mol / <6-ethoxy-2-chloro-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine and 22 g (0.28 mod) piperazine are stirred in ethanol at 40 ° C for 2 hours, then poured mixture to water, suction filter and recrystallize it from ethanol. This yields 13 g (93.8% of theory) of 6-ethoxy-2-chloro-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine with a melting point of 223-224 ° C. Product analysis : Formula C ^ H ^ gO ^ 7370.4 / Calculated: 45.39% C, 5.99% H, 8.66% S. Found: 45.30% C, 5.97% H, 8.56 % S. Example CII. 2,6-Di- / 1-OxydothiomorpholinM-mortfoMno-S-nitropyrimidine. This compound is prepared analogously to that described in example C, by reacting 2,6-di-di-K) -4-morpholine-5-nitropyrimidine with mp 129-130 ° C. from 1-oxydothiamorpholine in ethanol at 20 ° C. for 1 hour. The product melts at 250 ° C. Example CIII. 6-ethoxy-5-nitro-4-piperazine-2-thiomorpholinopyrimidine. This compound is prepared in a manner analogous to that described in example C, by reacting 6-ethoxy-4-cphiloro-5-nitro-'2-thiomorpholinopyrimidine with piperazine in ethanol at 78 ° C for 1 hour. The product melts at 84 ° C and 86 ° C (from isopropanol with ethyl acetate). Example CIV. 5-cyano-6-methoxy-4-piperazine-2-thiomortpholinopyrimidine. 18 g (0.067 mol) of 4-chloro-6-cyano-6-methoxy-2-thiomorpholinopyrimidine, mp 218-219 ° C, is mixed with 00.3 g of 70.7 imil / piperazine and heated for 3 hours at 130 ° C., then cooled, treated with water and extracted with chloroform. The extract is dried, evaporated with chlorophyll under reduced pressure, the residue is dissolved in hot ethanol and the solution is triturated with ethanolic hydrochloric acid, 5-cyano-6-methoxy-4-piperazine-2-thiomorpholine-pyrimidine hydrochloride. The precipitate is filtered off and washed with ethanol, yielding 13 g of 754.8% of theory (mp 261 ° C). Product analysis: Formula C, HgCINoOS (356.81). 36 Calculated: 47.18% C, 5.93% H, 23.52% N, 8.98% S. Found: 46.90% C, 5.90% H, 23.55% N, 8.96 % S. CV example. i6-ethoxy-5-nitro-2-piperazine-4- (1-oxydothiomorphplino) -pyrimidine. This compound is prepared by making 2 g of 76 mmoles (2,6-diethoxy-5-nitro-4-) 1-Oxydothio-morpholine / H-pyrimidine, mp 130-13 t 2 ° C and 8.6 g of 7100 millimoles / piperazine are heated at 125 ° C for 4 hours, then poured over ice, the precipitated crystalline product and recrystallizes it from ethanol. This gives 0.53 g of 723.6% of theory / product which melts at 221-2B2 ° C. Example CVI. 6-ethoxy-5-initro-4- (1-oxydothiomorpholine / -2-piperazinopyrimidine). 3.6 g / 0.0l mol / 6-ethoxy 5-nitro-2-piperazine-4-thiomorpholinopyrimidine is dissolved in 100 ml of methanol, treated with a solution of 2.2 g 70.01 mol / sodium methanadeate in 50 ml of water and refluxed for 4 hours, then poured the mixture into water and extracted with chloroform. The extract is dried, the chloroform is distilled off under reduced pressure and the residue is recrystallized from ethanol. The yield is 2.9 g of 777% of theory (6-ethoxy-5-nitro-4- (1-oxidothiomorpholine) -2-piperazinopyrimidine, mp 223-224 ° C. Example CVII. 6-ethoxy-5-nitro-4- (1-oxyothioformyl) -2-piperazinopyrimidine. 1 g (2.9 mmoles) of 6-ethoxy-2-methylsulfinyl-5-nitro-4- (1-o'xydothliomorpholinopyrimldine, mp 164-165 ° C, obtained by 6-ethoxy-2-reactions) -methylthio-5-nitro-4- (l-oxydothiomoitfo'lino-7-pyrimidine) with hydrogen peroxide in dilute acetic acid, mixed with 5 g of 40/58 mmoles / piperazine in 50 ml of ethanol and boiled for minutes under After reflux, pour the mixture into water and extract with chloroform. The extract was dried, evaporated to dryness and the residue was crystallized from ethanol, yielding 0.9 g of 784.7% of theoretical yield (6-ethoxy-5-nitro-4- (lHDxydothiomorpholine) -2-pi). Perazinopyrimidines, mp 220-222 ° C. Example CVIII. 6-ethoxy-5-nitro-4- (1-oxy-50 dotiomorpholine / -2-piperazinopyrimidine. This compound is prepared by making 1.2 g / 3 mmoles / 6-ethoxy-2- / N-formylpiperazine) (-5-nitro-4- (1-oxydothiomortfollino) pyrimidine, mp 209-211 ° C. and 1.2 g of 730 mmol / 55 sodium hydroxide in 80 ml of methanol are held for 3 hours. under reflux, then poured the mixture into water and extracted with chloroform. The extract was dried and the chloroform was evaporated in vacuo to give 1 g (89.6% of theory) of product which, upon recrystallization from ethanol, melts at 222 ° -223 ° C. Example CIX. 5-cyano-6-methoxy-fl-Z1-oxydothiomorpholineM-piperazine-65-pyrimidine hydrochloride 37 93 115 38 2.04 g / 0.01 mol / 5-cyano-2,4-dichloro-6-methoxypyrimidine o melting point 112 ° C is dissolved in 50 ml of dlyoxane, added to a solution of 2 g of potassium carbonate in 10 ml of water and cooled to 0 ° C, then a solution of 1.19 g / 0.01 mol is added dropwise while stirring and cooling. / 1-oxydothiomorpholine in 20 ml of dioxane. The 5-cyano-4-chloro-6-methoxy-2- (l-oxydothiomorpholine Z-pyrimidine) mixture is further reacted with 4.3 g / 0.05 mole / piperazine with stirring at room temperature for 3 hours. then added water and extracted with chloroform. The extract is dried with sodium sulfate, evaporated and the residue purified by column chromatography on Merck silica gel, 0.2-0.5 mm, eluting with a 10: 1 mixture of methanol and ammonia. The homogeneous fractions are pooled, evaporated to dryness, the residue dissolved in ethanol and the 5-cyano-6-methoxy-2- (1-oxyothiomorphyllin) -4-piperazinopyrimidine hydrochloride is precipitated by the addition of ethanolic hydrochloric acid. The yield is 2.2 g (59% of theory) of product which melts with signs of decomposition above 243 ° C. Product analysis: Formula C14H21GLN602S. (372.89) Calculated: 45.09% C, 5.67% H, 22.53% N. Found: 44.85% C, 5.57% H, 22.45% N. Example CX. 5-Cyano-2- (1,1-dioxydothio-morpholino / -6-methoxy-4-pilperazinopyrim; idine. This compound is prepared analogously to that described in example CXVII by the reaction -cyano-2,4-dichloro-6). -methoxypyrimidine, mp 112 ° C from 1,1-dioxydothiomorpholine and piperazine. The hydrochloride of this compound melts with decomposition at 237 ° C. Example CXI. 6-neopentyloxy-5-nitro-4- (1-oxydbthiomorpholino / -2-pliperazinopyrimidine). 4 - 5 g (0.011 mol) of O-neopentyloxy-5-nitro-2-pipazine-4-thiomorpholinopyrimidine is mixed with 60 ml of water and 11.4 ml (0.022 mol) of 2N hydrochloric acid and to the obtained 1.66 g (0.011 mole) of hydrogen peroxide were added to the suspension and the mixture was stirred at room temperature for 24 hours. The solution obtained is made alkaline by carefully adding 12 ml of 2N sodium hydroxide solution, the precipitate formed is filtered off, washed with water and crystallized from a mixture of 30 ml of methanol and 20 ml of water. The yield was 2.4 g (51.2% of theoretical yield) 6-neopentyloxy-5-nitro-4- (1-oixydothiomortpholine) -2-piperazinopyrimidine with a melting point of 156 ° C 158 ° C. Product analysis Formula C17H2 ^ NfiS /412.51/ Calculated: 49.50% C, 0.87% H, 20, 37% N, 7.77% S. Found: 49.30% C, 0.76% H, 20.43% N, 7.7 and 6% S. Example CXII. 2,6-diethoxy-5-n! Itro-4- (l-oxydothiomorpholino) -pyrimidine. 3.0 g of 793 mmoles of 6-chloro-2-methylthio-5-nitro -4- (1-oxydothiomorpholine) -pyrimidine, mp 12.8-131 ° C, are added at room temperature to the sodium ethoxide solution. , prepared from 0.22 g (0.0094 gram atom) of sodium and 3 µl of ethanol, the mixture was refluxed for 2 hours and then allowed to stand at room temperature for 20 hours. The mixture obtained is poured into water, extracted several times with chloroform and ethanol, the combined extracts are dried and evaporated to dryness. The residue was recrystallized from a mixture of ethyl acetate and petrol, yielding 2 g (65% of theory) (2,6-di-ethoxy-5-, nitro-4 -, 1-oxydol-Iiomorpholine) -pyrimidine, m.p. 130- 132 ° C. Product analysis: Formula C12H18Np5S /330.35/ Calculated: 43.63% C, 6.49% H, 16.96% N Found: 43.70% C, 5.38% H, 16 , 80% N. Example CXIII. 2- (N-carboethoxypiperazine / H6-methoxy-5-nitro-4-thiomoiifolinopyrimidine. This compound is prepared in a manner analogous to that described in Example 1 by the reactions of 2- (N-carboethoxypiperazine) -6-chloro-5 -nitro-4-thiomorpholinopryimidine, mp 134.5-136.5 ° C with sodium methoxide in methanol, in the presence of small amounts of dimethyl sulfoxide and potassium iodide. The reactions were carried out at 50 ° C. for 12 hours. The product crystallized with methanol melts at 158-1 (59 ° C. Example CXIV. 6-ethoxy-5-nitro-4- (1-oxy-thiomorpholine) -2-piperazinopyrimidine. To 3 ml of concentrated sulfuric acid is added 1 g of 6-ethoxy-2-p-perazine-4-thiomorphblinopyrimidine, the temperature of the resulting suspension rising to 50 ° C. After cooling to 0 ° C., 2 ml of concentrated nitric acid are added dropwise with stirring, and the mixture is stirred for 1 hour at temperature. the mixture is filtered through glass wool and the filtrate is mixed with ice water. Then, 40% sodium hydroxide solution is carefully added until the pH is 9 and extracted with chloroform. The extract is washed with water, dried with sodium sulphate and evaporated. solvent under reduced pressure. The residue was recrystallized from ethanol to give 0.8 g (66.9% of theory) of O-ethoxy-5-nitro-4- (1-oxydothliomorpholine) -2-p-perazinopyr - midins with a melting point of 223-B24 ° C. 45 Example CXV. 2 - (N-carlboxypropionylpyrimidine) -6-methyl-5-nitro-4- (1-oxidothiomorpholine) -pyrimidine. 3.4 g (0.01 mole) of 6-methyl-, 5-nitro-4- (1-oxydothiomorpholine) -2-piperazinopyrimidine, mp 170-178 ° C, obtained by the reaction with 2-chloro 6-methyl-5-liter-4- (1-oxydothiomorph] lino) -pyrimidine with piperazine in a mixture of acetone and dioxane, with the use of cooling, is dissolved in 200 ml of acetone, and a solution of 1.2 g (0.012) is slowly added with stirring. mole / succinic anhydride in 30 ml of acetone. After a few hours, the crystalline reaction product is allowed to drain off, washed with a small amount of ethanol in water (1: 1) and dried, giving 3.7 g of 4P (theoretical yield) (2- (N-carboxypropionyl)). piperazine (-6-methyl-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine. After recrystallization from efenol from water 71: 1, the product melts at 221 ° -223 ° C. 65 Example CXVI. 2- (N-acetoacetylpiperase-I $ 9no), 4-methyl-nitro-4R (1 -oxy * dotiQimrfoaiino) -pyrimidine. For a suspension of 3.4 g (0.11 mol) 6-methyl-5-nitro In about 40 ml of dioxane, a solution of 0.9 g (0.01 mole) of difcetone in 10 ml of dioxane is slowly added, while stirring and cooling, in 10 ml of dioxane. 1 hour at room temperature. The resulting clear solution is evaporated under reduced pressure and the oily residue is digested with a little ethyl acetate, and crystallization occurs after a short standing. The precipitate is filtered off, washed with a little methanol and dried, obtaining 3.9 g (92% of theoretical yield) (2- (N-acetoacetylpiperazine) -6-methyl-5-nitro-4- (1-oxydothiomorpholine). -pyrimidines. After a single recrystallization from methanol, the product melts at 174-176 ° C. Example CXVII. 6-Methyl-2- (N-nicotinyl-piperazine / -5-niitro-4- (1-oxydothiomoiifolin) -pyrimdine. For a solution of 3.5 g (0.02 mole) of nicotinic acid chloride in 60 ml of anhydrous pyridine is slowly added dropwise, while stirring at room temperature, a solution of 3.4 g of 70.01 mole (6-methyl-5-nItro-4- (1-oxydothiomorpholine) -2-piperazine-pyrimidine at room temperature. ml of pyridine, then stirred for 1 hour. Then the obtained solution is concentrated under reduced pressure to a low volume, the residue is dissolved in a small amount of water, and after a short persistence of the filtrate, the crystallized H-methyl-2- (N-liicotinoylpyrin) -5-nitro-4- / 1- -okaydottomorpholine-pyrimidine and immediately recrystallized from ethanol to give 3.4 g (76% of theory) of product, mp 145-148 ° C. Example CXVIII. 2- (N-isodicotinoylpiperazine / r6-methyl-5-nitro-4- (1-oxydothiomorphollino) - -pyrimidine. This compound is prepared in a manner analogous to that described in example CXVT by reactions (J, methylH5-nitro 4- (lfOxydothiomorpholine) -2-piperazinopyrimidine with isonicotinoyl chloride hydrochloride The product melts at 208 ° -aio ° c. Example CXJX. 6-methyl-5-nitro-4- (1-oxy-thymorlfoline) - 2- (N-salicylpiperazine) -primidine. This compound is prepared in an analogous manner to that described in example CXVI, from 6-methyl-5-nitro-4- (1-oxydothiomo-1rfoline) -2-piperazinopyrimidine and saldcyloyl chloride. The product melts at 143-146 ° C. Example CXX. 2 ^ [N- (2-furod'lo) -piperazine] -H6-methyl ^^ nitro-4W11-oxydothiomorph6l-plrimidine. This compound is prepared analogously. to the 6-methyl-5-nitro-4-N-α-tiomorthfolium (-2-piperazinopyrimidine) and furan-2-4 Laitononyl chloride dissolved in dioxane as described in Example 2, the product melts at temperature. J »Q ^ m ° C. Example CXXI. 2- (N, methoxyacetylpiperazine) -6-methyl-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine. 1115 40 This compound is prepared in an analogous manner to that described in Example CXVI, from 6-methyl-5-n; itro-4- (1-oxydothiomorpholine) &lt; 2 &gt; perazinopdrimidine and imethoxyacetyl chloride dissolved in dioxane. The product melts at 199-202 ° C. Example CXXII. 2- (N-carbamylpiperazine) -4- (1-oxy thiomorpholine) -5-nitro-6-methylflomer-captopyrimidine. 1.9 g of 2H-piperazino-4- (1-oxydothiomorpholm) -5-nitro-6-methylmercaptopyrimldine, m.p. 230 ° C, are dissolved in a mixture of 5 ml of glacial acetic acid and 10 ml of water and added dropwise to the solution in room temperature a solution of 2.0 g of potassium cyanate in 25 ml of water. Approximately 10 minutes after the end of the addition, the product begins to crystallize. The crude product was recrystallized from ethanol to give 1.3 g (62.7% of theory) (2- (N-canbamylpyrimidine) -4- (1-oxydothiomorpholine) -5- * iitro-6-methylomercaptopyrimidine. melts with decomposition at 204.0 ° C. Example CXXIII. 2- (N-methylcarbamylpyrimidine) -4- (1-oxydothiomorpholine) -5-nitro-6-methylmercaptopyrimidine. 1.8 g of 2-piperazine-4- / 1-oxydothiomorpholine? 5-nitro-6-methyl mercaptopyrimidine having a melting point of 230 ° C. are mixed in 20 ml of dioxane and a solution of 1 ml of methyl isocyanate is added dropwise within 5 minutes. After 10 minutes, three times the volume of water is added and the mixture is shaken with a mixture of equal amounts of chloroform and ethanol. The extract was evaporated and the residue was crystallized with acetone, yielding 33 2.02 g, 97.3% (theoretical yield) (2- (N-methyl-carfeamylpiperazine-M-) / 1-oxydothiomorpholine / -5-nitro-6-methylmercaptopyrimidine, melting with signs of decomposition at 265 ° C. Example CXXIV. 2-N, 2-dimethylcarbamino-piperazine (-4- (1-o'xydotdomorphoKno) -5-nitro-6-methylmercaptopyrimidine. 1.8 g of 2H-piperazine-4- (1-oxydothiomorpholine) -5-n (i-trio-6-methylmercaptopyrimidine, m.p. 230 ° C) is mixed with dioxane containing 1.0 g of triethylamine and to the obtained suspension 1.0 g of dimethylaminocartbamyl chloride is slowly added dropwise, heated to 50 ° C and heated for 30 minutes, the mixture becomes green in color. Then three 50 times the volume of water is poured, extracted with chloroform, the extract evaporated and the residue recrystallized. from acetone to obtain 2.1 g (98%) of theoretical yield (2- (N) dimethylcarbamylpiperazine) -4- (1-oxydothiomorpholne) HS-nitroJO-methylmercaptopyrimidine, mp 213-2B0 ° C Example CXXV. 2- (N-n-butyl-carbamylpiperazine) -4- (1-oloxydothiomoitfollino) - - 5-nitro -6-methylmercaptopyrimdine This compound is prepared in a manner analogous to that described in example CXXII , by the reaction of 1.0 g of 2-piperazine-4- (1-oxydothiomoitfoHmo / "5-nitro-6-methylmercaptopyrimidine melting point 230 ° C with 1.0 g of tert-butyl isocyanate. 1.2 g (94.8%) of theoretical yield (melting product at 2-1 ° C, 41 mt. : 45.95% C, 5.57% H, 17.86% N, 6.81% S. Found: 46.20% C, 5.78% H, 17.85% N, 6.79% S .Example CXXXI. 2- (N-nicotinoylpiperazine) -4- (1- O'xydothiomorpholine) -5-nitrc-6-methylomer-captopyrimidine. 2.6 g of 2-piperazine-4- (1-oxydotnomorpholine) -5-natro-6-methylmercaptopi-thymidine, m.p. 230 ° C, are mixed with 25 ml (of anhydrous pyridine and added to the suspension obtained in portions, while stirring). 87 g of nicotinic acid chloride hydrochloride, then stirred for 1 hour, the pyridine is distilled off, the residue is stirred with 100 ml of water for 3 hours, the precipitate is filtered off and recrystallized from isopropanol. 33.2% of the theoretical yield (2- (N-nicotinoylpyrazine) -4- (1-oxydothiomorpholine) -5-nitro-6-methylmercaptopyrimidine, which, after recrystallization from isopropanol, melts at 148-150 ° C C. Example CXXXII. 2- (N-donicotinoylpdphenosine) -4- (1-oxydothiomorpholine) - Nitro-6-methyl-meircaptopyrimidine. This compound is prepared analogously to that described in Example CXXX by reactions 2, 6 g of 2-piperazine-4- (1-oxydothiomorpholine) -5-nitro-6-methylmercaptopyrimdine, mp 230 ° C with 2.50 g of chlorohydride isondcotine orc. The yield is 17.5% theoretical, and the product recrystallized from isopropanol melts at 140-142 ° C. Example CXXXIII. 2- (N-carboxyacryloyl-piperazine Z-e-methyl-5-nitro-4- (1-oxydothiomorpholine) -pyrimidine. This compound is prepared in a manner analogous to that described in example CXIV by the reaction of 2-piperazine 5-nitro-4- (1) oxydothiomorpholine / pyrimidine with maleic anhydride. The product sinters at a temperature above 95 ° C. Product analysis: Formula CnH 2 O 2 S /438.5 / Calculated: 46.56% C, 5.05% H, 7.31% S. Found: 46.50% C, 6.32% H, 7.26% S. Example CXXVI. 2- / N-methoxymethylcarbamylpiperazineM- / 1-oxydothiomoTfolino / -5-nitro-6-methylmercaptopyrimidine * This compound is prepared analogously to that described in example CXXIII by reacting 1.8 g of 2-piperazine 4- / 1-Oxydothiomorpholino (-5-n-tro-6-methylmercaptopyrimidine, mp 230 ° C.) with 0.8 g of methoxymethyl isocyanate. 1.9 g (86% of theory) of melting product with signs of decomposition at 202-210 ° C are obtained. Example CXXVII. 2- (N-methylsaphonylpiperazine) -4- / 1-oxidothiomor (foline / -5-nitro-6-methyl-mercaptopyrimidine. This compound is prepared analogously to that described in example CXXIII by reacting 1.8 g 2 -piperazine-4- (1-oxydothiomore, lino) -5-nitro-6-methylmercaptopyrimidine, mp 230 ° C. with 1.0 g of methyl sulphoxide, in the presence of 1 g of triethylamine, 0 is obtained. , 9 g (40% of theory) of the product, m.p. 238-237 ° C. Example CXXVIII. 2- (tN-carboethoxypiperazine) -4- (1-oxydothiomorpholine) -5- (nitro-6-methylmercaptopyrimidine 4.0 g of 2- (N-carboethoxypiperazine) -4- (1-oxydothiomorpholine) -? 5-nitro-6-chloropyrimidine, mp 176-178 ° C, are dissolved in 10 ml of methanol and slowly added dropwise to a solution of 0.7 g of potassium ethanol in 40 ml of methanol treated with 1.5 ml of liquid methyl mercaptan Stir for 2 hours, diluted with 100 ml of water and extracted with chloroform. The extract is dried with sodium sulphate and evaporated. and the rest c is recrystallized from acetone to give 3.3 g (G9.1% of theory) of (2- (N-carboethoxypiperazine) -4- (1-oxydothiomorpholine) -5-nitro-6-methylmercapto-pyrimidine, m.p. 1911-196 ° C. Example CXXIX. 2- (N-acetoacetylpiperazine) -6-ethoxy-5-nitro-4- (1-o'xydothiomorpholane) - -pyrimidine This compound is prepared in a manner analogous to that described in example CXXV by 6-ethoxy- 5-n-trro-2-piperazine-4- (yl-oxydothiomosipholin) -pyrimidine, mp 223 ° -224 ° C with dichotone. The yield is 55% of theory, and the product recrystallized from ethanol melts at 191-192 ° C. Example CXXX. N- [6-ethoxy-5-nitro-4- (1-oxydothiomorthohydrin) -ptyrimidin-2-yl] -N- (3-carboxypropionyl) -piperazine. 3.75 g (0.01 mole) 6-ethoxy-5-nitro-4- (1-oxydothio-morphodino) -2-piperazinopyrimidine, m.p. 223-224 ° C and 2.0 g (0.02 mLa) The freshly distilled succinic anhydride is mixed with 50 ml of dioxane and refluxed for 1 hour, then evaporated to dryness and the solid residue recrystallized twice from a mixture of ethyl and propane. 2.0 g (42.5% of theory) of N, N, 3-ethoxy-5-nitro-4- (1-xydothiomorphoMno. Boxypropyl) -pipephazin, m.p. 1-8 ° 200 ° C. Pfoduct analysis: Formula d, B, F, S (470.51). PL PL PL PL PL PL

Claims (24)

1. Claims 1. Process for the preparation of the new pyrimidines of the general formula I, in which Si represents an alkoxy group with 1-3 carbon atoms, a morphoino group, a thiomonpholine group or a piperazine group which may be substituted in the 4 position by a formyl group - a carbamyl group or a kailboalkoxy group with 2 to 4 carbon atoms, H2 is a motpholinic, thiomorpholino or piperazine group, HB is a hydrogen, chlorine or bromine atom, a cyano group, and an ifarmylic orbacetyl group, and R4 is hydrogen, chlorine or phoromic, cyano or amino substituted with a pyrimidyl or phenyi-cyclohexyl radical; optionally having a chlorine atom, a carboxyl or a caribomethoxy group as a substituent, or R4 is also a 2- to 4-carbon carbohydrate group, an alkyl radical of 1-6 carbon atoms, optionally substituted with one or two carbon groups. 25 30 35 40 45 50 55 6093 115 43 m 2 to 4 carbon carboalkoxy, hydroxyl or mercapto, optionally substituted with an alkyl radical of 1 to 6 carbon atoms, and their physiologically acceptable addition salts with inorganic or organic acids, characterized in that the compound of formula II, in which R8 is as defined above, and one or two of X, Y and / or Z represent a convertible group, such as a halogen atom, a hydroxyl group, alkoxy or aryloxy, or a group of the formula —S — Q, —SO — O or —SO — O or —SO — Q, in which Q represents a hydrogen atom, an alkyl, aralkyl or aryl radical, and: the other substituents X, Y and / or Z are as defined above for Ri, R2 and R4, sub It is reacted with a compound of general formula III in which A is as defined for R1, R2 and / or R4 and the resulting compound of general formula I is optionally converted to a (physiologically acceptable addition salt with an inorganic or organic acid. 2. The method according to p. The process of claim 1, wherein the reactions are carried out in (a solvent. 3. The method according to p. The process of claim 1, wherein the reactions are carried out in the presence of an inorganic or organic tertiary base. 4. The method according to p. The process of claim 1, wherein the reactions are carried out at a temperature from -20 ° C to 2SO ° C. 5. A method for the preparation of the new pyrimidines of general formula 1, wherein R1 B1 and / or R4 is a free piperzyme group and R8 is hydrogen, chlorine or bromine, cyano, formyl or acetyl and R4 is hydrogen, chlorine or bromine, cyano or amine. substituted with a cyclohexyl, pyridyl or phenyl radical optionally substituted with a chlorine atom, a carboxyl or carbomethoxy group, or R4 is a carboalkoxy group with 2 to 4 carbon atoms, an alkyl radical with 1 to 6 carbon atoms, optionally substituted with one or two groups carboalkoxy with 2 to 4 carbon atoms, hydroxyl or mercapto, optionally substituted with an alkyl radical with 1 to 6 carbon atoms or 1-oxydothiomorpholine, and their physiologically acceptable addition salts with inorganic or organic acids, characterized by the compound of general formula II, in which Rs has the meaning given above and one or two of X, Y and / or Z represent a convertible group, such as a halogen atom, a hydroxyl, alkoxy or aryloxy group or a -S-Q, -SO-O or -SO-O or -SO-Q group in which Q represents a hydrogen atom, an alkyl, aralkyl or aryl radical, and the other substituents X, Y and / or Z are as defined above for R1f R2 and R4, reacted with a compound of general formula III, wherein A is as defined above for R1, Rf and / or R4, and then with a compound of general formula I The protecting group of the imino group in the compound of general formula II or the imino group in the compound of general formula III is split off during the reaction by hydrolysis in the presence of a base and the resulting compound of general formula 1 44 is optionally converted physiologically an inorganic or organic acid addition salt is acceptable. 6. The method according to p. 5. The process of claim 5, wherein the reactions are carried out in a solvent. 7. The method according to p. The process of claim 5, wherein the reactions are carried out in the presence of an inorganic or organic tertiary base. 8. The method according to p. 5. The process of claim 5, wherein the reactions are carried out at a temperature from -20 ° C to 250 ° C. 9. A method for the preparation of new pyrimidines of the general formula I, in which R1 is 1-oxydothiomorpholino or 1,1-dioxydothiomorpholino, R2 is 1-oxydothiomorpholino or 1,1-dioxydothiomorpholino, R8 is a hydrogen atom. ru, chlorine or bromine, cyano, formyl or acetyl, and R4 is hydrogen, chlorine or bromine, cyano or ammonium, substituted with a cyclohexyl, pyridyl or phenyl radical, optionally substituted chlorine, carboxyl or carbohydrate. methoxy or R4 is a carboxyalkoxy group of 2 to 4 carbon atoms, an alkyl radical of 1 to 6 carbon atoms, optionally substituted with one or two carboalkoxy groups of 2 to 4 carbon atoms, a hydroxyl group or a mer capto, optionally substituted with an alkyl radical of 1-6 carbon atoms or the 1-oxydothiorpholine group, and their physiologically acceptable addition salts with inorganic or organic acids, characterized by e a compound of general formula II in which R3 has the meaning given above and one or two of X, Y and / or Z is a convertible group such as halogen, hydroxy, alkoxy, uo or aryloxy or a group of formula —S — Q, —SO — O or —SO 2 — Q, wherein Q is a hydrogen atom, an alkyl, aralkyl or aryl radical, and the remaining X, Y and / or Z substituents represent a thiomorpholino group, are reacted with a compound of general formula III in which A is as defined above and the resulting compound is oxidized with an oxidizing agent and the resulting compound of general formula I is optionally converted into a physiologically acceptable addition salt with an inorganic or organic acid. 10. The method according to p. 9. The process of claim 9, wherein the reactions are carried out in a solvent. 50 11. The method according to p. 8. The process of claim 9, wherein the reactions are carried out in the presence of an inorganic base or a tertiary organic base. 12. The method according to p. 9. The process of claim 9, wherein the reactions are carried out at a temperature from -20 ° C to + 250 ° C. 13. A process for the preparation of new pyrimidines of general formula I, in which R4 represents a pyridinoyl group which may contain a pyridinoyl, furanoyl or salicylilyl group in the 4-position, or an alkanoyl group with 2 to 4 carbon atoms, a manually substituted acetyl, carboxyl or methoxy group, or which may contain at this position an aminocarbonyl group substituted with one or two alkyl radicals having 1-4 carbon atoms or a methylsulfonyl group, R2 is a piperazine group which in position 4 there may be a form or acetoacetyl group, R3 is nitro and R4 is hydrogen, methyl, methyl mercapto or ethoxy, and their physiologically acceptable inorganic or organic acid addition salts, characterized by that a compound of formula II, in which R8 is as defined above, one or two X, Y and / or Z represent a convertible group such as a halogen atom, a group hy droxy group, mercapto or sulfonic acid residue, substituted alkyl group, aralkyl ulb, aryl hydroxyl group, group (mercapto, sulfinyl or sulfonyl group, and the other substituents X, Y and / or Z 15 have the meaning given above for Ri, R2 and R4 are reacted with a compound of general formula 3 in which A is as defined above for R 1, R2 and / or R4 and the resulting compound of general formula 1 is optionally converted into its physiologically acceptable addition salt with an inorganic or organic acid. 14. The method according to p. The process of claim 13, wherein the reactions are carried out in a solvent. 15. The method according to p. The process of claim 13, wherein the reactions are carried out in the presence of an inorganic or tertiary organic base. 16. The method according to p. The process of claim 13, wherein the reactions are carried out at a temperature from -20 ° C to 250 ° C. thirty 17. A method for the preparation of new pyrimidines of general formula 1, wherein R ± and R2 are ipiperazine, substituted acyl or carfoamyl, R3 is nitro and R4 is hydrogen, methyl, methylomer-capto or ethoxy, and physiologically acceptable addition salts with inorganic or organic acids, characterized in that the compound of general formula II, in which R8 is as defined above, and one or two of X, Y and / or Z represent a convertible group such as a halogen atom, a hydroxyl group, a mercapto group or a sulfonic acid residue, a substituted alkyl, aralkyl or aryl hydroxyl group, a mercapto, sulfinyl or sulfonyl group, and the other X, Y and / or Z substituents are given above for R1, R2 and R4, are reacted with a compound of the general formula, in which A is as defined above for R1, R2 and / or R4, and the compound formed is then hydrolyzed, a compound containing a free imino group is acylated or carfoamylated and the resulting compound of general formula I is optionally converted into a physiologically acceptable addition salt with an inorganic or organic acid. 18. The method according to p. 17. The process of claim 17, wherein the reactions are carried out in a solvent. 19. The method according to claim 17. The process of claim 17, wherein the reactions are carried out in the presence of an inorganic or a tertiary organic base. 20. The method according to p. 17. The process according to claim 17, wherein the reactions are carried out at a temperature from -20 ° C to 250 ° C. 21. A method for the preparation of new pyrimidines of general formula I, in which R 1 represents a piperazine group which can be substituted in position 4 by a pyridinoyl, furanoyl, salicyloyl group, optionally substituted acetyl, carboxyl or methoxy alkali group. noyl group with 2 to 4 carbon atoms, optionally substituted methoxymethyl group or 1 or 2 alkyl groups with 1 to 4 carbon atoms, amino carbonyl group or methylsulfonyl group, R2 is piperazine which may be substituted in position 4. formyl or acetoacetyl, R3 is nitro, R4 is hydrogen, methyl, methylmercapto or ethoxy and their physiologically acceptable addition salts with inorganic or organic acids, characterized in that the compound of general formula II in which R3 is a hydrogen atom and one or two X, Y and / or Z represent a convertible group such as a halogen atom, a hydroxyl group, a mercapto group or a sulfonic acid residue, a substituted alkyl, aralkyl or aryl hydroxyl group, mercapto, sulfinyl or sulfonyl group, and the other X, Y and / or substituents are as defined above for R1. R2 and R4 are reacted with a compound of formula III in which A is as defined above for R15, R2 and / or R4, and the compound formed is nitrated with a nitrating agent such as a mixture of sulfuric acid and nitric acid. or nitric acid, at elevated temperatures, preferably 50-80 ° C., and the resulting nitro compound of general formula I is optionally converted into a physiologically acceptable addition salt with an inorganic or organic acid. 22. The method according to claim The process of claim 21, wherein the reactions are carried out in a solvent. 23. The method according to claim The process of claim 31, wherein the reactions are carried out in the presence of an inorganic base or a tertiary organic base. 24. The method according to claim 21, characterized in that the reactions are carried out at a temperature of -20 ° C - 250 ° C. 93115 R_WZdR 1; -N MODEL 2 H-A WZdR 3 Bltk 1430/77 r. 110 copies A4 Price PLN 10 PL PL PL PL PL PL